鼻咽癌T7噬菌体cDNA文库的构建和鼻咽癌血清自身抗体的筛选
|
摘要
鼻咽癌(Nasopharyngeal carcinoma,NPC)是一种上皮源性的高发于我国南方及东南亚一带的头颈部恶性肿瘤,在我国广东、广西、福建、湖南、江西尤为突出,据估计全世界鼻咽癌病例中80%发生于我国,年发病率为10-25/10万。由于鼻咽癌起病隐匿,部位特殊,早期症状缺乏特异性,导致早期诊断十分困难,通常在鼻咽癌确诊时,70%以上的患者局部已经高度恶性或扩散到淋巴结,已属于临床中晚期。因此,早期诊断鼻咽癌将极大提高鼻咽癌的治愈率和提高患者预后。
许多蛋白质在肿瘤组织中高表达,这些蛋白质能刺激机体的免疫系统产生抗体,这些自身抗体比肿瘤蛋白质更容易检测,因此将常规检测这些高表达的蛋白质改为检测肿瘤患者体内针对这些肿瘤相关抗原的自身抗体是一种更有效的策略。相当部分的自身抗体作为肿瘤的诊断和预后判断的指标有着潜在的价值,如抗BRD2和α-甲基-辅酶A消旋酶(alpha-methylacyl-CoA racemase,AMACR)自身抗体用于前列腺癌的诊断,抗Annexin XI-A和Grb2相关蛋白自身抗体用于乳腺癌的诊断,抗表皮细胞粘附分子(Epithelial cell adhesion molecule,Ep-CAM)和肌酸激酶B(creatine kinase B,CKB)自身抗体用于卵巢癌的诊断等。目前在鼻咽癌中也发现了一些高表达的蛋白质,如fibronectin、Mac-2BP、plasminogen、和zinc-alpha(2)-glycoprotein(ZAG)等,提示一系列的针对这些高表达蛋白质的自身抗体有可能用于鼻咽癌的诊断和监测,具有很高的应用价值。因此研究针对鼻咽癌特异性或者相关性肿瘤抗原的自身抗体将大大提高鼻咽癌的诊断效率,这些自身抗体有望作为鼻咽癌的肿瘤标志物。
首先,探讨了鼻咽癌患者血清中是否存在抗鼻咽癌自身抗原的抗体,为寻找鼻咽癌新的肿瘤标志物提供依据。以Epstein-Barr病毒阴性的鼻咽癌细胞株CNE1细胞为固相抗原板,酶联免疫吸附实验(ELISA)分析其与32例鼻咽癌患者血清和54例正常血清反应的差异性;提取CNE1总蛋白,Western印迹分析其与鼻咽癌患者血清反应是否存在特异性的蛋白质。
ELISA分析结果显示鼻咽癌患者血清平均OD_(405)值(0.904±0.032)明显高于正常人血清平均OD_(405)值(0.736±0.028)(P＜0.01);Western印迹分析发现鼻咽癌患者血清与正常人血清相比,部分阳性条带位置一致,但条带阳性强度增加,还发现出现了部分新的阳性条带,这些条带可能属于鼻咽癌相关抗原或鼻咽癌特异性抗原。说明鼻咽癌患者血清中存在抗鼻咽癌自身抗原的抗体,这些抗体并非针对Epstein-Barr病毒,为寻找鼻咽癌血清肿瘤标志物提供了依据。
其次,用8例病理确诊的鼻咽癌组织活检标本构建鼻咽癌T7噬菌体cDNA文库,然后再利用来源于鼻咽癌临床分期在Ⅱ-Ⅳ期患者的血清和正常人血清进行生物淘洗,并将生物淘洗获得的22个噬菌体重组蛋白进行免疫印迹和ELISA实验鉴定。随后通过ELISA分析鼻咽癌患者和正常人血清中的5个抗噬菌体重组蛋白自身抗体的水平,ROC分析这些自身抗体作为鼻咽癌诊断标志物的特异性和敏感性。
结果成功构建了鼻咽癌混合组织T7噬菌体cDNA文库,原始库容量为8.0×10~7pfu/ml,放大后的库容量为3.47×10~(10)pfu/ml,为生物淘洗奠定了基础。利用鼻咽癌患者血清和正常人血清经生物淘洗分离了31个肿瘤相关蛋白质,DNA序列分析显示这31个蛋白质中有22个为独立的与已知或者假定的蛋白质相匹配。说明通过生物淘洗能有效富集与鼻咽癌患者血清发生反应的蛋白质,而这些蛋白质不与正常人血清发生反应,为进一步实验提供了依据。
RT-PCR检测发现BMI-1基因在7株不同的鼻咽癌细胞株中均有不同程度的表达,而在正常鼻咽上皮细胞株NP69中不表达。随后以BMI-1噬菌体重组蛋白与鼻咽癌患者血清进行免疫印迹分析,结果显示在不同的鼻咽癌患者血清中存在不同滴度的抗BMI-1自身抗体,且抗BMI-1自身抗体与BMI-1具有良好的亲合力。进一步ELISA检测鼻咽癌血清中抗BMI-1自身抗体的水平,发现在鼻咽癌患者血清中,抗BMI-1自身抗体平均OD_(405)值为0.791±0.025,而在正常人血清中平均OD_(405)值为0.488±0.042,统计学分析二者之间具有显著性差异(P＜0.01)。ROC分析曲线下面积为0.8044,说明抗BMI-1自身抗体作为鼻咽癌诊断的标志物,具有良好的特异性和敏感性。以鼻息肉患者血清为对照,进一步分析抗BMI-1自身抗体与鼻咽癌临床资料之间的关系,发现抗BMI-1自身抗体与鼻咽癌的转移有密切关系,在原位鼻咽癌患者血清中的水平与鼻息肉患者血清水平相比,具有显著性差异(P＜0.01),提示抗BMI-1自身抗体有可能作为鼻咽癌的早期诊断标志物。
在探讨抗BMI-1自身抗体作为鼻咽癌标志物的基础上,又进一步检测了抗CD44、MAGE、fibronectin、HSP70和EBNA-1的自身抗体。CD44、MAGE、fibronectin和HSP70均能与不同的鼻咽癌患者血清发生反应,这种反应强度与正常人血清比较,具有明显差异(P＜0.05)。ELISA分析显示抗CD44、MAGE、fibronectin和HSP70的自身抗体具有与4个人噬菌体蛋白良好的亲合力,在鼻咽癌患者血清中的水平明显高于正常人血清和鼻息肉患者血清中的水平(P＜0.05),而在正常人血清和鼻息肉患者血清中的水平无明显差异(P＞0.05),进一步为以抗CD44、MAGE、fibronectin和HSP70的自身抗体作为鼻咽癌的标志物提供了依据。
ROC分析抗CD44、MAGE、fibronectin和HSP70自身抗体作为鼻咽癌标志物的ROC曲线下面积分别为0.7857、0.8922、0.8091和0.8435,而抗EBNA-1自身抗体作为鼻咽癌诊断标志物的ROC分析曲线下面积为0.6110,说明抗CD44、MAGE、fibronectin和HSP70的自身抗体作为鼻咽癌诊断的标志物,其特异性和敏感性均高于抗EBNA-1自身抗体作为鼻咽癌诊断的标志物。
进一步分析抗CD44、MAGE、fibronectin和HSP70自身抗体是否可以作为鼻咽癌早期诊断的标志物,显示鼻咽癌患者血清中抗MAGE自身抗体水平与鼻咽癌的临床分期紧密相关,抗CD44、fibronectin和HSP70的自身抗体的水平也与鼻咽癌的临床分期相关,提示抗MAGE自身抗体可能作为鼻咽癌早期诊断的标志物,这些鼻咽癌患者血清自身抗体的水平可以用来预测鼻咽癌的临床分期。
总之,通过本研究,证实了在鼻咽癌患者血清中存在针对鼻咽癌组织的自身抗体,这些自身抗体有可能作为鼻咽癌的肿瘤标志物,用于鼻咽癌的早期诊断或者预后判断,但是由于这些自身抗体也存在于其它肿瘤患者血清中,所以难以单独用于鼻咽癌的诊断,而将多个自身抗体联合起来用于鼻咽癌的早期诊断是有可能的。
Nasopharyngeal carcinoma (NPC) is one of the most common cancers in the Chinese and other Asian populations. It is one of the serious health problems in Southern China where an annual incidence of more than 20 cases per 100,000 was reported. Metastasis was found in 7% of the patients at the time of initial diagnosis and 20% or more developed metastasis after treatment. However, NPC is often diagnosed late due to its deep location and vague symptoms. Therefore, a diagnostic assay that can detect NPC early would greatly improve the treatment outcome of NPC.
Many proteins are overexpressed in tumor tissues, which could activate the immune system to produce their antibodies. Instead of measuring the levels of these over expressed proteins, an alternative approach is to measure the circulating antibodies against tumor-associate -d proteins in the sera of patients. Some autoantibodies could have diagnostic and prognostic value, such as antibodies against BRD2 and alpha-methylacyl-CoA racemase (AMACR) for prostate cancer, antibodies against annexin XI-A and Grb2-associated protein 2 for breast cancer, and antibodies against the epithelial cell adhesion molecule (Ep-CAM) and creatine kinase B for ovarian cancer. There were also several overexpressed proteins that could be used as potential tumor markers for NPC, such as fibronectin, Mac-2 binding protein, plasminogen, inter-α-trypsin inhibitor precursor and zinc-alpha(2)-glycoprotein (ZAG). These observations strongly suggested that a list of potential autoantibody markers will greatly facilitate the development of an assay with high predictive value. Studies of the autoantibodies in NPC patients towards these NPC specific antigens could provide an effective diagnostic assay for NPC. Autoantibody signatures, as new biomarkers, may improve the early detection of nasopharyngeal carcinoma.
At first, in this study, to investigate whether there are autoantibodies to NPC in the patients sera in order to find new nasopharyngeal carcinoma(NPC) biomarker, we prepared the cell plate of Epstein Barr-virus negative NPC cell line CNE1, and analyzed the differential reactions between 32 NPC patient serum and 54 normal serum by ELISA. Extracted the total protein of CNE1, and analyzed whether had the specific proteins to react with NPC serum by Western blot.
The results of ELISA showed that the average of NPC patients sera antibody absorbance values(0.904±0.032) were significantly elevated above the mean of normal sera antibody absorbance values (0.736±0.028) (P<0.01). The analysis with Western blot showed there were positive bands ,and some of these were unanimously bands, but the intensity increased, and some of these were new bands compared with normal serum. These positive bands may be NPC tumor-associated antigens or NPC tumor-specific antigens. There are autoantibodies reacted with NPC in the sera of patients with NPC, and which not reacted with Epstein-Barr virus. It provided the basis to seek the tumor biomarkers in NPC serum.
Secondly, to construct a T7 phage cDNA library from mixed nasopharyngeal carcinoma tissue samples of 8 patients using Novagen's OrientExpress cDNA Synthesis and Cloning Systems, and biopan the T7 phage cDNA library with sera pooled from ten NPC patients (stages II-IV) and from normal healthy donors. Twenty two phage expressed immunogenic proteins were identified through immunochemical detection and ELISA. Then we measured the levels of autoantibodies against five identified proteins in the sera of NPC patients and in the sera of healthy donors by ELISA to evaluate the sensitivity and specificity of these autoantibodies for NPC detection. Logistic regression was used to evaluate the probability of a sample to be the serum of a patient or the serum of a health donor.
We constructed a T7 phage cDNA library from mixed NPC tissues, and we isolated 31 tumor-associated proteins using biopan enrichment techniques with sera from NPC patients and from healthy population. DNA sequence analysis showed that among 31 phage-displayed proteins, 22 have sequence identity with known or putative tumor-associated proteins. The results of immunochemical reactivity of patients' sera with phage expressed proteins showed enrichment in the number of immunogenic phage clones in the biopanning process and also confirmed that antibodies were present in the sera of patients but not in the sera of healthy donors.
The phage expressing BMI-1 protein was isolated by screening of a mixture of nasopharyngeal carcinoma (NPC) cDNA T7 phage library and found that the antibody against BMI-1 was elevated in the sera from NPC patients. BMI-1 mRNA was over-expressed at different levels in seven NPC cell lines compared with normal nasopharyngeal epithelial cell line NP69. Histochemistry showed that patient sera were more reactive with BMI-1 than normal sera. Antibody affinity assay using sera from 40 NPC patients and 54 controls showed that BMI-1 antibody was significantly greater in patient sera than in normal controls (patient 0.791±0.025 and normal 0.488±0.042; P<0.001) and the BMI-1 autoantibody be significantly related with the progress of NPC (Benign versus LNPC P=0.001; LNPC versus MNPC P=0.047). Analysis of the results with logistic regression and receiver operating characteristics (ROC) curves showed that BMI-1 antibody was a modest marker for NPC (sensitivity 0.74 and specificity 0.73;AUC=0.8044). The showed that BMI-1 antibody as a potential marker of NPC may be rational, and could have diagnostic and prognostic value.
We measured the levels of antibodies against another four phage expressed proteins and the phage expressed protein EBNA-1. The c statistic (i.e., area under the curve) of EBNA-1, which is the positive control, was 0.6110 (P=0.0120). MAGE was the most significant with a c statistic of 0.8922 (P<0.0001). The c statistic of HSP70 was 0.8435 (P<0.0001), the c statistic of CD44 was 0.7857 (P<0.0001), and the c statistic of fibronectin was 0.8091 (P<0.0001). These results showed that phage expressed proteins, HSP70, CD44, fibronectin and MAGE, as markers had greater sensitivity and specificity to predict the NPC disease than EBNA-1.
There was a significant correlation between the levels of HSP70, CD44, fibronectin or MAGE antibodies with the clinical stage (P < 0.001) in the NPC groups. The autoantibody level of MAGE positively correlated with T classification: higher T classification correlated with higher autoantibody levels of MAGE(P<0.05). And the antibody levels against other three proteins partially correlated with the clinical stages of NPC. The levels of antibodies can be used to predict the clinical stages of NPC.
Our studies suggested that the autoantibodies against tumor-associ -ated antigens in the sera of NPC patients could be used as a screening test for NPC and these autoantibodies can be used for the early detection of NPC. Studies of the corresponding proteins may have significances in tumor biology, novel drug development, and immunotherapy. However, analysis of more serum samples is needed to improve the statistical power and to validate this method as a clinically reliable assay. Efficient alternatives detected by ELISA could facilitate development of a blood test for NPC prediction. Testing a full panel of antibodies specific for NPC will be an important part of assay validation and eventually defines the clinical applicability.
In summary, we identified immunogenic proteins and their autoantibodies in peripheral blood and generated a panel of antibody markers, which could have significant diagnostic, therapeutic and scientific values.
许多蛋白质在肿瘤组织中高表达,这些蛋白质能刺激机体的免疫系统产生抗体,这些自身抗体比肿瘤蛋白质更容易检测,因此将常规检测这些高表达的蛋白质改为检测肿瘤患者体内针对这些肿瘤相关抗原的自身抗体是一种更有效的策略。相当部分的自身抗体作为肿瘤的诊断和预后判断的指标有着潜在的价值,如抗BRD2和α-甲基-辅酶A消旋酶(alpha-methylacyl-CoA racemase,AMACR)自身抗体用于前列腺癌的诊断,抗Annexin XI-A和Grb2相关蛋白自身抗体用于乳腺癌的诊断,抗表皮细胞粘附分子(Epithelial cell adhesion molecule,Ep-CAM)和肌酸激酶B(creatine kinase B,CKB)自身抗体用于卵巢癌的诊断等。目前在鼻咽癌中也发现了一些高表达的蛋白质,如fibronectin、Mac-2BP、plasminogen、和zinc-alpha(2)-glycoprotein(ZAG)等,提示一系列的针对这些高表达蛋白质的自身抗体有可能用于鼻咽癌的诊断和监测,具有很高的应用价值。因此研究针对鼻咽癌特异性或者相关性肿瘤抗原的自身抗体将大大提高鼻咽癌的诊断效率,这些自身抗体有望作为鼻咽癌的肿瘤标志物。
首先,探讨了鼻咽癌患者血清中是否存在抗鼻咽癌自身抗原的抗体,为寻找鼻咽癌新的肿瘤标志物提供依据。以Epstein-Barr病毒阴性的鼻咽癌细胞株CNE1细胞为固相抗原板,酶联免疫吸附实验(ELISA)分析其与32例鼻咽癌患者血清和54例正常血清反应的差异性;提取CNE1总蛋白,Western印迹分析其与鼻咽癌患者血清反应是否存在特异性的蛋白质。
ELISA分析结果显示鼻咽癌患者血清平均OD_(405)值(0.904±0.032)明显高于正常人血清平均OD_(405)值(0.736±0.028)(P＜0.01);Western印迹分析发现鼻咽癌患者血清与正常人血清相比,部分阳性条带位置一致,但条带阳性强度增加,还发现出现了部分新的阳性条带,这些条带可能属于鼻咽癌相关抗原或鼻咽癌特异性抗原。说明鼻咽癌患者血清中存在抗鼻咽癌自身抗原的抗体,这些抗体并非针对Epstein-Barr病毒,为寻找鼻咽癌血清肿瘤标志物提供了依据。
其次,用8例病理确诊的鼻咽癌组织活检标本构建鼻咽癌T7噬菌体cDNA文库,然后再利用来源于鼻咽癌临床分期在Ⅱ-Ⅳ期患者的血清和正常人血清进行生物淘洗,并将生物淘洗获得的22个噬菌体重组蛋白进行免疫印迹和ELISA实验鉴定。随后通过ELISA分析鼻咽癌患者和正常人血清中的5个抗噬菌体重组蛋白自身抗体的水平,ROC分析这些自身抗体作为鼻咽癌诊断标志物的特异性和敏感性。
结果成功构建了鼻咽癌混合组织T7噬菌体cDNA文库,原始库容量为8.0×10~7pfu/ml,放大后的库容量为3.47×10~(10)pfu/ml,为生物淘洗奠定了基础。利用鼻咽癌患者血清和正常人血清经生物淘洗分离了31个肿瘤相关蛋白质,DNA序列分析显示这31个蛋白质中有22个为独立的与已知或者假定的蛋白质相匹配。说明通过生物淘洗能有效富集与鼻咽癌患者血清发生反应的蛋白质,而这些蛋白质不与正常人血清发生反应,为进一步实验提供了依据。
RT-PCR检测发现BMI-1基因在7株不同的鼻咽癌细胞株中均有不同程度的表达,而在正常鼻咽上皮细胞株NP69中不表达。随后以BMI-1噬菌体重组蛋白与鼻咽癌患者血清进行免疫印迹分析,结果显示在不同的鼻咽癌患者血清中存在不同滴度的抗BMI-1自身抗体,且抗BMI-1自身抗体与BMI-1具有良好的亲合力。进一步ELISA检测鼻咽癌血清中抗BMI-1自身抗体的水平,发现在鼻咽癌患者血清中,抗BMI-1自身抗体平均OD_(405)值为0.791±0.025,而在正常人血清中平均OD_(405)值为0.488±0.042,统计学分析二者之间具有显著性差异(P＜0.01)。ROC分析曲线下面积为0.8044,说明抗BMI-1自身抗体作为鼻咽癌诊断的标志物,具有良好的特异性和敏感性。以鼻息肉患者血清为对照,进一步分析抗BMI-1自身抗体与鼻咽癌临床资料之间的关系,发现抗BMI-1自身抗体与鼻咽癌的转移有密切关系,在原位鼻咽癌患者血清中的水平与鼻息肉患者血清水平相比,具有显著性差异(P＜0.01),提示抗BMI-1自身抗体有可能作为鼻咽癌的早期诊断标志物。
在探讨抗BMI-1自身抗体作为鼻咽癌标志物的基础上,又进一步检测了抗CD44、MAGE、fibronectin、HSP70和EBNA-1的自身抗体。CD44、MAGE、fibronectin和HSP70均能与不同的鼻咽癌患者血清发生反应,这种反应强度与正常人血清比较,具有明显差异(P＜0.05)。ELISA分析显示抗CD44、MAGE、fibronectin和HSP70的自身抗体具有与4个人噬菌体蛋白良好的亲合力,在鼻咽癌患者血清中的水平明显高于正常人血清和鼻息肉患者血清中的水平(P＜0.05),而在正常人血清和鼻息肉患者血清中的水平无明显差异(P＞0.05),进一步为以抗CD44、MAGE、fibronectin和HSP70的自身抗体作为鼻咽癌的标志物提供了依据。
ROC分析抗CD44、MAGE、fibronectin和HSP70自身抗体作为鼻咽癌标志物的ROC曲线下面积分别为0.7857、0.8922、0.8091和0.8435,而抗EBNA-1自身抗体作为鼻咽癌诊断标志物的ROC分析曲线下面积为0.6110,说明抗CD44、MAGE、fibronectin和HSP70的自身抗体作为鼻咽癌诊断的标志物,其特异性和敏感性均高于抗EBNA-1自身抗体作为鼻咽癌诊断的标志物。
进一步分析抗CD44、MAGE、fibronectin和HSP70自身抗体是否可以作为鼻咽癌早期诊断的标志物,显示鼻咽癌患者血清中抗MAGE自身抗体水平与鼻咽癌的临床分期紧密相关,抗CD44、fibronectin和HSP70的自身抗体的水平也与鼻咽癌的临床分期相关,提示抗MAGE自身抗体可能作为鼻咽癌早期诊断的标志物,这些鼻咽癌患者血清自身抗体的水平可以用来预测鼻咽癌的临床分期。
总之,通过本研究,证实了在鼻咽癌患者血清中存在针对鼻咽癌组织的自身抗体,这些自身抗体有可能作为鼻咽癌的肿瘤标志物,用于鼻咽癌的早期诊断或者预后判断,但是由于这些自身抗体也存在于其它肿瘤患者血清中,所以难以单独用于鼻咽癌的诊断,而将多个自身抗体联合起来用于鼻咽癌的早期诊断是有可能的。
Nasopharyngeal carcinoma (NPC) is one of the most common cancers in the Chinese and other Asian populations. It is one of the serious health problems in Southern China where an annual incidence of more than 20 cases per 100,000 was reported. Metastasis was found in 7% of the patients at the time of initial diagnosis and 20% or more developed metastasis after treatment. However, NPC is often diagnosed late due to its deep location and vague symptoms. Therefore, a diagnostic assay that can detect NPC early would greatly improve the treatment outcome of NPC.
Many proteins are overexpressed in tumor tissues, which could activate the immune system to produce their antibodies. Instead of measuring the levels of these over expressed proteins, an alternative approach is to measure the circulating antibodies against tumor-associate -d proteins in the sera of patients. Some autoantibodies could have diagnostic and prognostic value, such as antibodies against BRD2 and alpha-methylacyl-CoA racemase (AMACR) for prostate cancer, antibodies against annexin XI-A and Grb2-associated protein 2 for breast cancer, and antibodies against the epithelial cell adhesion molecule (Ep-CAM) and creatine kinase B for ovarian cancer. There were also several overexpressed proteins that could be used as potential tumor markers for NPC, such as fibronectin, Mac-2 binding protein, plasminogen, inter-α-trypsin inhibitor precursor and zinc-alpha(2)-glycoprotein (ZAG). These observations strongly suggested that a list of potential autoantibody markers will greatly facilitate the development of an assay with high predictive value. Studies of the autoantibodies in NPC patients towards these NPC specific antigens could provide an effective diagnostic assay for NPC. Autoantibody signatures, as new biomarkers, may improve the early detection of nasopharyngeal carcinoma.
At first, in this study, to investigate whether there are autoantibodies to NPC in the patients sera in order to find new nasopharyngeal carcinoma(NPC) biomarker, we prepared the cell plate of Epstein Barr-virus negative NPC cell line CNE1, and analyzed the differential reactions between 32 NPC patient serum and 54 normal serum by ELISA. Extracted the total protein of CNE1, and analyzed whether had the specific proteins to react with NPC serum by Western blot.
The results of ELISA showed that the average of NPC patients sera antibody absorbance values(0.904±0.032) were significantly elevated above the mean of normal sera antibody absorbance values (0.736±0.028) (P<0.01). The analysis with Western blot showed there were positive bands ,and some of these were unanimously bands, but the intensity increased, and some of these were new bands compared with normal serum. These positive bands may be NPC tumor-associated antigens or NPC tumor-specific antigens. There are autoantibodies reacted with NPC in the sera of patients with NPC, and which not reacted with Epstein-Barr virus. It provided the basis to seek the tumor biomarkers in NPC serum.
Secondly, to construct a T7 phage cDNA library from mixed nasopharyngeal carcinoma tissue samples of 8 patients using Novagen's OrientExpress cDNA Synthesis and Cloning Systems, and biopan the T7 phage cDNA library with sera pooled from ten NPC patients (stages II-IV) and from normal healthy donors. Twenty two phage expressed immunogenic proteins were identified through immunochemical detection and ELISA. Then we measured the levels of autoantibodies against five identified proteins in the sera of NPC patients and in the sera of healthy donors by ELISA to evaluate the sensitivity and specificity of these autoantibodies for NPC detection. Logistic regression was used to evaluate the probability of a sample to be the serum of a patient or the serum of a health donor.
We constructed a T7 phage cDNA library from mixed NPC tissues, and we isolated 31 tumor-associated proteins using biopan enrichment techniques with sera from NPC patients and from healthy population. DNA sequence analysis showed that among 31 phage-displayed proteins, 22 have sequence identity with known or putative tumor-associated proteins. The results of immunochemical reactivity of patients' sera with phage expressed proteins showed enrichment in the number of immunogenic phage clones in the biopanning process and also confirmed that antibodies were present in the sera of patients but not in the sera of healthy donors.
The phage expressing BMI-1 protein was isolated by screening of a mixture of nasopharyngeal carcinoma (NPC) cDNA T7 phage library and found that the antibody against BMI-1 was elevated in the sera from NPC patients. BMI-1 mRNA was over-expressed at different levels in seven NPC cell lines compared with normal nasopharyngeal epithelial cell line NP69. Histochemistry showed that patient sera were more reactive with BMI-1 than normal sera. Antibody affinity assay using sera from 40 NPC patients and 54 controls showed that BMI-1 antibody was significantly greater in patient sera than in normal controls (patient 0.791±0.025 and normal 0.488±0.042; P<0.001) and the BMI-1 autoantibody be significantly related with the progress of NPC (Benign versus LNPC P=0.001; LNPC versus MNPC P=0.047). Analysis of the results with logistic regression and receiver operating characteristics (ROC) curves showed that BMI-1 antibody was a modest marker for NPC (sensitivity 0.74 and specificity 0.73;AUC=0.8044). The showed that BMI-1 antibody as a potential marker of NPC may be rational, and could have diagnostic and prognostic value.
We measured the levels of antibodies against another four phage expressed proteins and the phage expressed protein EBNA-1. The c statistic (i.e., area under the curve) of EBNA-1, which is the positive control, was 0.6110 (P=0.0120). MAGE was the most significant with a c statistic of 0.8922 (P<0.0001). The c statistic of HSP70 was 0.8435 (P<0.0001), the c statistic of CD44 was 0.7857 (P<0.0001), and the c statistic of fibronectin was 0.8091 (P<0.0001). These results showed that phage expressed proteins, HSP70, CD44, fibronectin and MAGE, as markers had greater sensitivity and specificity to predict the NPC disease than EBNA-1.
There was a significant correlation between the levels of HSP70, CD44, fibronectin or MAGE antibodies with the clinical stage (P < 0.001) in the NPC groups. The autoantibody level of MAGE positively correlated with T classification: higher T classification correlated with higher autoantibody levels of MAGE(P<0.05). And the antibody levels against other three proteins partially correlated with the clinical stages of NPC. The levels of antibodies can be used to predict the clinical stages of NPC.
Our studies suggested that the autoantibodies against tumor-associ -ated antigens in the sera of NPC patients could be used as a screening test for NPC and these autoantibodies can be used for the early detection of NPC. Studies of the corresponding proteins may have significances in tumor biology, novel drug development, and immunotherapy. However, analysis of more serum samples is needed to improve the statistical power and to validate this method as a clinically reliable assay. Efficient alternatives detected by ELISA could facilitate development of a blood test for NPC prediction. Testing a full panel of antibodies specific for NPC will be an important part of assay validation and eventually defines the clinical applicability.
In summary, we identified immunogenic proteins and their autoantibodies in peripheral blood and generated a panel of antibody markers, which could have significant diagnostic, therapeutic and scientific values.
引文
[1]Bui Quoc H,Buu-Hoi NP,Phan Ngoc D,et al.Nasopharyngeal cancers in Vietnam:epidemiology,clinical aspects,possible etiologic factors.Ann Otolaryngol Chir Cervicofac.1969;86(4):267-278.
[2]姚开泰.从死因回顾调查资料看湖南省鼻咽癌流行病学的一些特点并探索其发病机理.中南大学学报(医学版).1982;7(1):10-17.
[3]黄腾波,陈德林,黄惠明,等.鼻咽癌在不同高发区人群中的发病差异.癌症.1998;17(2):84-86.
[4]Boussen H,Bouaouina N,Mokni-Baizig N,et al.Nasopharyngeal carcinoma.Recent data.Pathol Biol(Paris).2005;53(1):45-51.
[5]Chan AT,Teo PM,Johnson PJ.Nasopharyngeal carcinoma.Ann Oncol.2002;13(7):1007-1015.
[6]Yu MC,Yuan JM.Epidemiology of nasopharyngeal carcinoma.Semin Cancer Biol.2002;12(6):421-429.
[7]Chan AT,Teo PM,Huang DP.Pathogenesis and treatment of nasopharyngeal carcinoma.Semin Oncol.2004;31(6):794-801.
[8]Lin JC,Wang WY,Chen KY,et al.Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma.N Engl J Med.2004;350(24):2461-2470.
[9]Marcy PY,Zhu Y,Bensadoun RJ.Target volumes in radiotherapy - head and neck tumors intensity-modulated radiation therapy(IMRT)of nasopharyngeal carcinoma:practical aspects in the delineation of target volumes and organs at risk.Cancer Radiother.2005;9(4):240-250.
[10]Lee N,Puri DR,Blanco A.I,et al.Intensity-modulated radiation therapy in head and neck cancers:an update.Head Neck.2007;29(4):387-400.
[11]Ma BB,Chan AT.Recent perspectives in the role of chemotherapy in the management of advanced nasopharyngeal carcinoma.Cancer.2005;103(1):22-31.
[12]Chan AT,Teo PM,Leung TW,et al.The role of chemotherapy in the management of nasopharyngeal carcinoma.Cancer.1998;82(6):1003-1012.
[13]Chong VF.Tumour volume measurement in head and neck cancer.Cancer Imaging.2007;7 Spec No A:S47-49.
[14]Jeyakumar A,Brickman TM,Jeyakumar A,et al.Review of nasopharyngeal carcinoma. Ear Nose Throat J. 2006;85(3):168-170,172-163,184.
[15] Kristensen CA, Specht LK. Combined chemotherapy and radiotherapy in patients with nasopharyngeal cancer. A survey of a Cochrane review. Ugeskr Laeger. 2008;170(6):430-433.
[16] O'Sullivan B. Nasopharynx cancer: therapeutic value of chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2007;69(2 Suppl):S118-121.
[17] King AD, Ma BB, Yau YY, et al. The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis. Br J Radiol. 2008;81(964):291-298.
[18] Cho WC. Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer. 2007;6:1.
[19] Caron M, Choquet-Kastylevsky G, Joubert-Caron R. Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics. 2007;6(7):1115-1122.
[20] Toubi E, Shoenfeld Y. Protective autoimmunity in cancer (review). Oncol Rep. 2007;17(1):245-251.
[21] Tiwawech D, Srivatanakul P, Karalak A, et al. Cytochrome P450 2A6 polymorphism in nasopharyngeal carcinoma. Cancer Lett. 2006;241(1):135- 141.
[22] Jiang JH, Li Z, Su G, et al. [Study on genetic polymorphisms of CYP2F1 gene in Guangdong population of China]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23(4):383-387.
[23] Cao Y, Miao XP, Huang MY, et al. Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population. BMC Cancer. 2006;6:167.
[24] Catarino RJ, Breda E, Coelho V, et al. Association of the A870G cyclin D1 gene polymorphism with genetic susceptibility to nasopharyngeal carcinoma. Head Neck. 2006;28(7):603-608.
[25] Xiao B, Fan S, Zeng Z, et al. Purification of novel UBAP1 protein and its decreased expression on nasopharyngeal carcinoma tissue microarray. Protein Expr Purif. 2006;47(1):60-67.
[26] Chow LS, Lam CW, Chan SY, et al. Identification of RASSF1A modulated genes in nasopharyngeal carcinoma. Oncogene. 2006;25(2):310-316.
[27] Lo PH, Xie D, Chan KC, et al. Reduced expression of RASSF1A in esophag -eal and nasopharyngeal carcinomas significantly correlates with tumor stage. Cancer Lett. 2007;257(2): 199-205.
[28] Soejima H, Kawamoto S, Akai J, et al. Isolation of novel heart-specific genes using the BodyMap database. Genomics. 2001;74(1): 115-120.
[29] Zhang SQ, Peng H, Song LY, et al. Detection of KIAA1173 gene expression in nasopharyngeal carcinoma tissues and cell lines on tissue microarray. Ai Zheng. 2005;24(11): 1322-1326.
[30] Sun D, Zhang Z, Van do N, et al. Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker. Oral Oncol. 2007;43(1):82-87.
[31] Wu CC, Chien KY, Tsang NM, et al. Cancer cell-secreted proteomes as a basis for searching potential tumor markers: nasopharyngeal carcinoma as a model. Proteomics. 2005;5(12):3173-3182.
[32] Wong BC, Chan KC, Chan AT, et al. Reduced plasma RNA integrity in nasopharyngeal carcinoma patients. Clin Cancer Res. 2006; 12(8):2512-2516.
[33] Lung HL, Bangarusamy DK, Xie D, et al. THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma. Oncogene. 2005;24(43):6525-6532.
[34]. Yau WL, Lung HL, Zabarovsky ER, et al. Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma. Int J Cancer. 2006; 119(12):2821-2826.
[35] Peng D, Ren CP, Yi HM, et al. Genetic and epigenetic alterations of DLC-1, a candidate tumor suppressor gene, in nasopharyngeal carcinoma. Acta Biochim Biophys Sin (Shanghai). 2006;38(5):349-355.
[36] Qiu GH, Tan LK, Loh KS, et al. The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene. 2004;23(27):4793-4806.
[37]. Ying J, Srivastava G, Hsieh WS, et al. The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors. Clin Cancer Res. 2005; 11(18):6442-6449.
[38] Geara FB, Sanguineti G, Tucker SL, et al. Carcinoma of the nasopharynx treated by radiotherapy alone:determinants of distant metastasis and survival.Radiother Oncol.1997;43(1):53-61.
[39]Shi X,Yuan X,Tao D,et al.Analysis of DNA ploidy,cell cycle and Ki67antigen in nasopharyngeal carcinoma by flow cytometry.J Huazhong Univ Sci Technolog Med Sci.2005;25(2):198-201.
[40]Zhao GQ,Xu Y,Wang Q.Significance of serum vascular endothelial growth factor test before radiotherapy in patients with nasopharyngeal carcinoma.Zhong Xi Yi Jie He Xue Bao.2005;3(4):274-277.
[41]Cho WC,Yip TT,Yip C,et al.Identification of serum amyloid a protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling.Clin Cancer Res.2004;10(1 Pt 1):43-52.
[42]Cho WC,Yip TT,Ngan RK,et al.ProteinChip array profiling for identific -ation of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma.Clin Chem.2007;53(2):241-250.
[43]Minard ME,Kim LS,Price JE,et al..The role of the guanine nucleotide exchange factor Tiaml in cellular migration,invasion,adhesion and tumor progression.Breast Cancer Res Treat.2004;84(1):21-32.
[44]Mo L,Wang H,Huang G,et al.Correlation between expression of the Tiaml gene and the invasion and metastasis in nasopharyngeal carcinoma.Lin Chuang Er Bi Yan Hou Ke Za Zhi.2005;19(17):785-787.
[45]Horikawa T,Kaizaki Y,Kato H,et al.Expression of interleukin-8 receptor A predicts poor outcome in patients with nasopharyngeal carcinoma.Laryngoscope.2005;115(1):62-67.
[46]Tee YT,Chen GD,Lin LY,et al.Nm23-H1:a metastasis-associated gene.Taiwan J Obstet Gynecol.2006;45(2):107-113.
[47]Jiang WZ,Liao YP,Zhao SP,et al.Expression clinical significance of nm23-H1 and vessel endothelium growth factor protein in nasopharyngeal carcinoma.Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi.2006;41(3):200-204.
[48]Tsang CW,Lin X,Gudgeon NH,et al.CD4+ T-cell responses to Epstein-Barr virus nuclear antigen EBNA1 in Chinese populations are highly focused on novel C-terminal domain-derived epitopes.J Virol.2006;80(16):8263-8266.
[49]Fachiroh J,Paramita DK,Hariwiyanto B,et al.Single-assay combination of Epstein-Barr Virus(EBV)EBNA1-and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G(IgG)and IgA antibody levels in sera from nasopharyngeal carcinoma patients:options for field screening.J Clin Microbiol.2006;44(4):1459-1467.
[50]Tarbouriech N,Ruggiero F,de Turenne-Tessier M,et al.Structure of the Epstein-Barr virus oncogene BARF1.J Mol Biol.2006;359(3):667-678.
[51]Swissa M,Amital-Teplizki H,Haim N,et al.Autoantibodies in neoplasia.An unresolved enigma.Cancer.1990;65(11):2554-2558.
[52]Bidoli E,Villalta D,Battistin M,et al.Epidemiological and ethical aspects of multiplex autoantibody testing.Autoimmun Rev.2007;6(6):354-358.
[53]Amos MD,Bridges AJ.Standards for autoantibody testing;addressing future needs for autoimmune disease and cancer diagnosis.Cancer Biomark.2005;1(4-5):221-227.
[54]Cho-Chung YS.Autoantibody biomarkers in the detection of cancer.Biochim Biophys Acta.2006;1762(6):587-591.
[55]Finn OJ.Immune response as a biomarker for cancer detection and a lot more.N Engl J Med.2005;353(12):1288-1290.
[56]Tan EM.Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis.J Clin Invest.2001;108(10):1411-1415.
[57]Admon A,Shoshan SH.Antibodies as oncogenes:a hypothesis.Med Hypotheses.2006;67(3):471-473.
[58]Sahin U,Tureci O,Schmitt H,et al.Human neoplasms elicit multiple specific immune responses in the autologous host.Proc Natl Acad Sci U S A.1995;92(25):11810-11813.
[59]Lee SY,Obata Y,Yoshida M,et al.Immunomic analysis of human sarcoma.Proc Natl Acad Sci U S A.2003;100(5):2651-2656.
[60]Preuss KD,Zwick C,Bormann C,et al.Analysis of the B-cell repertoire against antigens expressed by human neoplasms.Immunol Rev.2002;188:43-50.
[61]Nesterova M,Johnson N,Cheadle C,et al.Autoantibody biomarker opens a new gateway for cancer diagnosis.Biochim Biophys Acta.2006;1762(4):398-403.
[62]Lennon VA,Kryzer TJ,Griesmann GE,et al.Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes.N Engl J Med.1995;332(22):1467-1474.
[63]Spuler S,Sarropoulos A,Marx A,et al.Thymoma-associated myasthenia gravis.Transplantation of thymoma and extrathymomal thymic tissue into SCID mice.Am J Pathol.1996;148(5):1359-1365.
[64]Gordon PA,Baylis PH,Bird GW.Tumour-induced autoimmune haemolytic anaemia.Br Med J.1976;1(6025):1569-1570.
[65]Bellone JD,Kunicki TJ,Aster RH.Immune thrombocytopenia associated with carcinoma.Ann Intern Med.1983;99(4):470-472.
[66]Kruskall MS,Weitzman SA,Stossel TP,et al.Lymphoma with autoimmune neutropenia and hepatic sinusoidal infiltration:a syndrome.Ann Intern Med.1982;97(2):202-205.
[67]Fishman P,Merimski O,Baharav E,et al.Autoantibodies to tyrosinase:the bridge between melanoma and vitiligo.Cancer.1997;79(8):1461-1464.
[68]Sigurgeirsson B,Lindelof B,Edhag O,et al.Risk of cancer in patients with dermatomyositis or polymyositis.A population-based study.N Engl J Med.1992;326(6):363-367.
[69]Kinlen LJ.Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment.Am J Med.1985;78(1A):44-49.
[70]Bematsky S,Clarke A,Ramsey-Goldman R.Malignancy and systemic lupus erythematosus.Curr Rheumatol Rep.2002;4(4):351-358.
[71]Ruiz-Irastorza G,Ugarte A,Egurbide MV,et al.Antimalarials may influence the risk of malignancy in systemic lupus erythematosus.Ann Rheum Dis.2007;66(6):815-817.
[72]Abu-Shakra M,Gladman DD,Urowitz MB.Malignancy in systemic lupus erythematosus.Arthritis Rheum.1996;39(6):1050-1054.
[73]Tzioufas AG,Boumba DS,Skopouli FN,et al.Mixed monoclonal cryoglobu -linemia and monoclonal rheumatoid factor cross-reactive idiotypes as predictive factors for the development of lymphoma in primary Sjogren's syndrome.Arthritis Rheum.1996;39(5):767-772.
[74]Zatuchni J,Campbell WN,Zarafonetis CJ.Pulmonary fibrosis and terminal bronchiolar(alveolar-cell)carcinoma in scleroderma.Cancer.1953;6(6):1147-1158.
[75]Okayasu I,Fujiwara M,Hara Y,et al.Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma.A study of surgical cases among Japanese,and white and African Americans.Cancer.1995;76(11):2312-2318.
[76]Swissa M,Cohen Y,Shoenfeld Y.Autoantibodies in the sera of patients with lymphoma.Leuk Lymphoma.1992;7(1-2):117-122.
[77]Thomas PJ,Kaur JS,Aitcheson CT,et al.Antinuclear,antinucleolar,and anticytoplasmic antibodies in patients with malignant melanoma.Cancer Res.1983;43(3):1372-1380.
[78]Twomey JJ,Rossen RD,Lewis VM,et al.Rheumatoid factor and tumor-host interaction.Proc Natl Acad Sci U S A.1976;73(6):2106-2108.
[79]Manz RA,Hauser AE,Hiepe F,et al.Maintenance of serum antibody levels.Annu Rev Immunol.2005;23:367-386.
[80]Hamano Y,Tsukamoto K,Abe M,et al.Genetic dissection of vasculitis,myeloperoxidase-specific antineutrophil cytoplasmic autoantibody production,and related traits in spontaneous crescentic glomerulonephritis-forming/Kinjoh mice.J Immunol.2006;176(6):3662-3673.
[81]Lemieux R,Bazin R.Autoantibody-induced formation of immune complexes in normal human serum.Curr Pharm Des.2006;12(2):173-179.
[82]Plotz PH.The autoantibody repertoire:searching for order.Nat Rev Immunol.2003;3(1):73-78.
[83]Wardemann H,Yurasov S,Schaefer A,et al.Predominant autoantibody production by early human B cell precursors.Science.2003;301(5638):1374-1377.
[84]Gay D,Saunders T,Camper S,et al.Receptor editing:an approach by autoreactive B cells to escape tolerance.J Exp Med.1993;177(4):999-1008.
[85]Tiegs SL,Russell DM,Nemazee D.Receptor editing in self-reactive bone marrow B cells.J Exp Med.1993;177(4):1009-1020.
[86]Goodnow CC,Crosbie J,Adelstein S,et al.Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice.Nature.1988;334(6184):676-682.
[87]Nemazee DA,Burki K.Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class Ⅰ antibody genes.Nature.1989;337(6207):562-566.
[88]Tiller T,Tsuiji M,Yurasov S,et al.Autoreactivity in human IgG+ memory B cells.Immunity.2007;26(2):205-213.
[89]Ding C,Yan J.Regulation of autoreactive B cells:checkpoints and activation.Arch Immunol Ther Exp(Warsz).2007;55(2):83-89.
[90] Etzioni R, Urban N, Ramsey S, et al. The case for early detection. Nat Rev Cancer. 2003;3(4):243-252.
[91] Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006;56(1):11-25; quiz 49-50.
[92] Chen YT, Gure AO, Tsang S, et al. Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci U S A. 1998;95(12):6919-6923.
[93] Scanlan MJ, Gure AO, Jungbluth AA, et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002; 188:22-32.
[94] Scanlan MJ, Welt S, Gordon CM, et al. Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets. Cancer Res. 2002;62(14):4041-4047.
[95] Schmitz-Winnenthal FH, Galindo-Escobedo LV, Rimoldi D, et al. Potential target antigens for immunotherapy in human pancreatic cancer. Cancer Lett. 2007;252(2):290-298.
[96] Seliger B, Kellner R. Design of proteome-based studies in combination with serology for the identification of biomarkers and novel targets. Proteomics. 2002;2(12): 1641-1651.
[97] Naour FL, Brichory F, Beretta L, et al. Identification of tumor-associated antigens using proteomics. Technol Cancer Res Treat. 2002;1(4):257-262.
[98] Hardouin J, Lasserre JP, Sylvius L, et al. Cancer immunomics: from serological proteome analysis to multiple affinity protein profiling. Ann N Y Acad Sci. 2007; 1107:223-230.
[99] Le Naour F, Misek DE, Krause MC, et al. Proteomics-based identification of RS/DJ-1 as a novel circulating tumor antigen in breast cancer. Clin Cancer Res. 2001;7(11):3328-3335.
[100] Sarkissian G, Fergelot P, Lamy PJ, et al. Identification of Pro-MMP-7 as a Serum Marker for Renal Cell Carcinoma by Use of Proteomic Analysis. Clin Chem.2008;54(3):574-581.
[101] Unwin RD, Harnden P, Pappin D, et al. Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics. 2003;3(1):45-55.
[102] Prasannan L, Misek DE, Hinderer R, et al. Identification of beta-tubulin isoforms as tumor antigens in neuroblastoma. Clin Cancer Res. 2000;6(10): 3949-3956.
[103] Klade CS, Voss T, Krystek E, et al. Identification of tumor antigens in renal cell carcinoma by serological proteome analysis. Proteomics. 2001;l(7):890- 898.
[104] Lichtenfels R, Kellner R, Atkins D, et al. Identification of metabolic enzymes in renal cell carcinoma utilizing PROTEOMEX analyses. Biochim Biophys Acta.2003;1646(1-2):21-31.
[105] Seliger B, Menig M, Lichtenfels R, et al. Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy. Proteomics. 2003;3(6):979-990.
[106] Huang Y, Franklin J, Gifford K, et al. A high-throughput proteo-genomics method to identify antibody targets associated with malignant disease. Clin Immunol. 2004;111(2):202-209.
[107] Velculescu VE, Zhang L, Vogelstein B, et al. Serial analysis of gene expression. Science. 1995;270(5235):484-487.
[108] Caron M, Joubert-Caron R, Canelle L, et al. Serological Proteome Analysis (SERPA) and Multiple Affinity Protein Profiling (MAPPING) to Discover Cancer Biomarkers. Mol Cell Proteomics. 2005;4(8):s142.
[109] Hardouin J, Duchateau M, Canelle L, et al. Thiophilic adsorption revisited. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;845(2):226-231.
[110] Yin H, Killeen K, Brennen R, et al. Microfluidic chip for peptide analysis with an integrated HPLC column, sample enrichment column, and nanoelectrospraytip. Anal Chem. 2005;77(2):527-533.
[111] Brennen RA, Yin H, Killeen KP. Microfluidic gradient formation for nanoflow chip LC. Anal Chem. 2007;79(24):9302-9309.
[112] Chen YT. Cancer vaccine: identification of human tumor antigens by SEREX. Cancer J. 2000;6 Suppl 3:S208-217.
[113] Jager D. Potential target antigens for immunotherapy identified by serological expression cloning (SEREX). Methods Mol Biol. 2007;360:319-326.
[114] Jalbout M, Bel Hadj Jrad B, Bouaouina N, et al. Autoantibodies to tubulin are specifically associated with the young age onset of the nasopharyngeal carcinoma. Int J Cancer. 2002;101(2): 146-150.
[115] Lamelin JP, de-The G, Revillard JP, et al. Autoantibodies (cold lymphocy-totoxins, antiactin antibodies and antinuclear factors) in nasopharyngeal carcinoma patients. IARC Sci Publ. 1978(20):523-536.
[116] Henle W, Henle G, Lanier AP, et al. Attachment of antinuclear antibodies to nasopharyngeal carcinoma or other cells during preparation of biopsy imprints. J Natl Cancer Inst. 1986;76(6): 1041-1046.
[117] Takimoto T, Ishikawa S, Masuda K, et al. Antinuclear antibodies in the sera of patients with nasopharyngeal carcinoma. Am J Otolaryngol. 1989;10(6):399- 403.
[118] Bel Hadj Jrad B, Mahfouth W, Bouaouina N, et al. A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction. Cancer Lett. 2006;233(1):21-27.
[119] Sapir T, Blank M, Shoenfeld Y. Immunomodulatory effects of intravenous immunoglqbulins as a treatment for autoimmune diseases, cancer, and recurrent pregnancy loss. Ann N Y Acad Sci. 2005;1051:743-778.
[120] Fernandez Madrid F. Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis. Cancer Lett. 2005;230(2): 187-198.
[121] Himoto T, Kuriyama S, Zhang JY, et al. Analyses of autoantibodies against tumor-associated antigens in patients with hepatocellular carcinoma. Int J Oncol. 2005;27(4): 1079-1085.
[122] Conry RM, Allen KO, Lee S, et al. Human autoantibodies to carcinoe -mbryonic antigen (CEA) induced by a vaccinia-CEA vaccine. Clin Cancer Res.2000;6(1):34-41.
[123] Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl J Med. 2005;353(12): 1224-1235.
[124] King, A. Autoantibodies as novel biomarkers for the early detection of prostate cancer. Nat Clin Pract Oncol. 2006;3(1):7-8.
[125] Carlizzi G, Ciarla MV, Di Luzio A, et al. Autoantibodies in patients with monoclonal gammopathies. Ann N Y Acad Sci. 2007; 1107:206-211.
[126] Marchalonis JJ, Schluter SF, Sepulveda RT, et al. Immunomodulation by immunopeptides and autoantibodies in aging, autoimmunity, and infection. Ann N Y Acad Sci. 2005; 1057:247-259.
[127] Kutok JL, Wang F. Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol. 2006; 1:375-404.
[128] Hecht JL, Aster JC. Molecular biology of Burkitt's lymphoma. J Clin Oncol. 2000;18(21):3707-3721.
[129] Imai S, Koizumi S, Sugiura M, et al. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci U S A. 1994;91(19):9131-9135.
[130] Sugiura M, Imai S, Tokunaga M, et al. Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. Br J Cancer. 1996;74(4):625-631.
[131] McClain KL, Leach CT, Jenson HB, et al. Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med. 1995;332(1):12-18.
[132] Chang Y, Cheng SD, Tsai CH. Chromosomal integration of Epstein-Barr virus genomes in nasopharyngeal carcinoma cells. Head Neck. 2002;24(2): 143-150.
[133] Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228(4705):1315-1317.
[134] Jimenez J, Santisteban A, Carazo JM, et al. Computer graphic display method for visualizing three-dimensional biological structures. Science. 1986;232 (4754):1113-1115.
[135] Gershoni JM, Roitburd-Berman A, Siman-Tov DD, et al. Epitope mapping: the first step in developing epitope-based vaccines. BioDrugs. 2007;21(3):145- 156.
[136] Sidhu SS, Koide S. Phage display for engineering and analyzing protein interaction interfaces. Curr Opin Struct Biol. 2007; 17(4) :481-487.
[137] Scheuermann J, Dumelin CE, Melkko S, et al. DNA-encoded chemical libraries. J Biotechnol. 2006;126(4):568-581.
[138] Diamond SL. Methods for mapping protease specificity. Curr Opin Chem Biol. 2007;11(1):46-51.
[139] Sergeeva A, Kolonin MG, Molldrem JJ, et al. Display technologies: application for the discovery of drug and gene delivery agents. Adv Drug Deliv Rev. 2006;58(15): 1622-1654.
[140] Kehoe JW, Kay BK. Filamentous phage display in the new millennium. Chem Rev. 2005;105(11):4056-4072.
[141] Hoess RH. Bacteriophage lambda as a vehicle for peptide and protein display. Cun Pharm Biotechnol. 2002;3(1):23-28.
[142] Shivachandra SB, Li Q, Peachman KK, et al. Multicomponent anthrax toxin display and delivery using bacteriophage T4. Vaccine. 2007;25(7): 1225-1235.
[143] Cerritelli ME, Conway JF, Cheng N, et al. Molecular mechanisms in bacteriophage T7 procapsid assembly, maturation, and DNA containment. Adv Protein Chem. 2003 ;64:301-323.
[144] Kalnina Z, Silina K, Meistere I, et al. Evaluation of T7 and lambda phage display systems for survey of autoantibody profiles in cancer patients. J Immunol Methods. 2008. (in print)
[145] Chen J, Xu XM, Underhill CB, et al. Tachyplesin activates the classic complement pathway to kill tumor cells. Cancer Res. 2005;65(11):4614-4622.
[146] Nowak JE, Chatterjee M, Mohapatra S, et al. Direct production and purification of T7 phage display cloned proteins selected and analyzed on microarrays. Biotechniques. 2006;40(2):220-227.
[147] Roman I, Figys J, Steurs G, et al. Direct measurement of VDAC-actin interaction by surface plasmon resonance. Biochim Biophys Acta. 2006; 1758(4):479-486.
[148] Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. Cancer Res. 2007; 67(7):3461-3467.
[149] Sheu TJ, Schwarz EM, Martinez DA, et al. A phage display technique identifies a novel regulator of cell differentiation. J Biol Chem. 2003;278(1): 438-443.
[150] Zhong L, Peng X, Hidalgo GE, et al. Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients. Cancer Detect Prev. 2003;27(4):285-290.
[151] Conroy SE, Sasieni PD, Fentiman I, et al. Autoantibodies to the 90kDa heat shock protein and poor survival in breast cancer patients. Eur J Cancer. 1998;34(6):942-943.
[152] Trieb K, Gerth R, Windhager R, et al. Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma. Immunobiology. 2000;201(3-4):368-376.
[153] Trieb K, Gerth R, Holzer G, et al. Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. Br J Cancer. 2000;82(1):85-87.
[154] Fujita Y, Nakanishi T, Miyamoto Y, et al. Proteomics-based identification of autoantibody against heat shock protein 70 as a diagnostic marker in esophageal squamous cell carcinoma. Cancer Lett. 2008.(in print)
[155] Conroy SE, Sasieni PD, Amin V, et al. Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer. Br J Cancer. 1998;77(11):1875-1879.
[156] Stockert E, Jager E, Chen YT, et al. A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med. 1998;187(8): 1349-1354.
[157] Fernandez-Madrid F, Tang N, Alansari H, et al. Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer. Cancer Res. 2004;64(15):5089-5096.
[158] Pelucchi A, Ciceri E, Clementi F, et al. Calcium channel autoantibodies in myasthenic syndrome and small cell lung cancer. Am Rev Respir Dis. 1993; 147(5): 1229-1232.
[159] Lang B, Evoli A. SOX1 autoantibodies: tumor markers in LEMS patients? Neurology. 2008;70( 12):906-907.
[160] Rennert G Prevention and early detection of colorectal cancer—new horizons. Recent Results Cancer Res. 2007;174:179-187.
[161] Karakiewicz PI, Perrotte P, McCormack M, et al. Early detection of prostate cancer with ultrasound-guided systematic needle biopsy. Can J Urol. 2005; 12 Suppl 2:5-8.
[162] Vlastos G, Verkooijen HM. Minimally invasive approaches for diagnosis and treatment of early-stage breast cancer. Oncologist. 2007;12(1):1-10.
[163] Cassidy A, Duffy SW, Myles JP, et al. Lung cancer risk prediction: a tool for early detection. Int J Cancer. 2007;120(1):1-6.
[164] Sasco AJ. Screening of undifferentiated carcinoma of the nasopharynx. Bull Cancer. 1996;83(5):344-351.
[165] Taweevisit M. Overexpression of p53 and neoplastic cell proliferation in undifferentiated nasopharyngeal carcinoma. Southeast Asian J Trop Med Public Health. 2007;38(1): 136-140.
[166] Chan KC, Lo YM. Clinical applications of plasma Epstein-Barr virus DNA analysis and protocols for the quantitative analysis of the size of circulating Epstein-Barr virus DNA.Methods Mol Biol.2006;336:111-121.
[167]Heinzelmann-Schwarz VA,Gardiner-Garden M,Henshall SM,et al.Overexpression of the cell adhesion molecules DDR1,Claudin 3,and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer.Clin Cancer Res.2004;I0(13):4427-4436.
[168]Huddleston HG,Wong KK,Welch WR,et al.Clinical applications of microarray technology:creatine kinase B is an up-regulated gene in epithelial ovarian cancer and shows promise as a serum marker.Gynecol Oncol.2005;96(1):77-83.
[169]Bachelot T,Ratel D,Menetrier-Caux C,et al.Autoantibodies to endostatin in patients with breast cancer:correlation to endostatin levels and clinical outcome.Br J Cancer.2006;94(7):1066-1070.
[170]Hanahan D,Weinberg RA.The hallmarks of cancer.Cell.2000;100(1):57-70.
[171]Song LB,Zeng MS,Liao WT,et al.Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells.Cancer Res.2006;66(12):6225-6232.
[172]Ma BB,Leungrn SF,Hui EP,et al.Prospective validation of serum CYFRA 21-1,beta-2-microglobulin,and ferritin levels as prognostic markers in patients with nonmetastatic nasopharyngeal carcinoma undergoing radiotherapy.Cancer.2004;101(4):776-781.
[173]Ho DW,Yang ZF,Wong BY,et al.Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry serum protein profiling to identify nasopharyngeal carcinoma.Cancer.2006;107(1):99-107.
[174]Emoto K,Yamada Y,Sawada H,et al.Annexin Ⅱ overexpression correlates with stromal tenascin-C overexpression:a prognostic marker in colorectal carcinoma.Cancer.2001;92(6):1419-1426.
[175]Lee KD,Lee HH,Joo HB,et al.Expression of MAGE A 1-6 mRNA in sputa of head and neck cancer patients—a preliminary report.Anticancer Res.2006;26(2B):1513-1518.
[176]Mambula SS,Calderwood SK.Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes.J Immunol.2006;177(11):7849-7857.
[177]Liu R,Wang X,Chen GY,et al.The prognostic role of a gene signature from tumorigenic breast-cancer cells.N Engl J Med.2007;356(3):217-226.
[178] Adams JM, Cory S. Oncogene co-operation in leukaemogenesis. Cancer Surv. 1992;15:119-141.
[179] Liebermann DA, Hoffman B. Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation. Stem Cells. 1994;12(4):352-369.
[180] Gorrini C, Squatrito M, Luise C, et al. Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature. 2007;448(7157): 1063-1067.
[181] Raaphorst FM. Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1. Trends Immunol. 2003;24(10):522-524.
[182] Liu S, Dontu G, Wicha MS. Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 2005;7(3):86-95.
[183] van Lohuizen M, Verbeek S, Scheijen B, et al. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991;65(5):737-752.
[184] Haupt Y, Alexander WS, Barri G, et al. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991;65(5):753-763.
[185] van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999- 2009.
[186] Mihara K, Chowdhury M, Nakaju N, et al. Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis. Blood. 2006;107(1):305-308.
[187] Breuer RH, Snijders PJ, Sutedja GT, et al. Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions. Lung Cancer. 2005;48(3):299-306.
[188] Merkerova M, Bruchova H, Kracmarova A, et al. Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia transformation. Leuk Lymphoma. 2007;48(4):793-801.
[189] Yoshizaki T, Wakisaka N, Kondo S, et al. Treatment of locally recurrent epstein-barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir.J Med Virol.2008;80(5):879-882.
[190]Seto E,Ooka T,Middeldorp J,et al.Reconstitution of nasopharyngeal carcinoma-type EBV infection induces tumorigenicity.Cancer Res.2008;68(4):1030-1036.
[191]Pathmanathan R,Prasad U,Chandrika G,et al.Undifferentiated,nonkeratiniz -ing,and squamous cell carcinoma of the nasopharynx.Variants of Epstein-Barr virus-infected neoplasia.Am J Pathol.1995;146(6):1355-1367.
[192]Tam JS,Murray HG.Nasopharyngeal carcinoma and Epstein-Barr virus associated serologic markers.Ear Nose Throat J.1990;69(4):261-267.
[193]Deyrup AT.Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.Hum Pathol.2008;39(4):473-483.
[194]Buccheri GF,Violante B,Sartoris AM,et al.Clinical value of a multiple biomarker assay in patients with bronchogenic carcinoma.Cancer.1986;57(12):2389-2396.
[195]Buccheri G,Ferrigno D.Serum biomarkers of non-neuron-endocrine origin in small-cell lung cancer:a 16-year study on carcinoembryonic antigen,tissue polypeptide antigen and lactate dehydrogenase.Lung Cancer.2000;30(1):37-49.
[196]Pectasides D,Bafaloucos D,Antoniou F,et al.TPA,TATI,CEA,AFP,beta-HCG,PSA,SCC,and CA 19-9 for monitoring transitional cell carcinoma of the bladder.Am J Clin Oncol.1996;19(3):271-277.
[1]Markowska J.Tumor makrers in cervical cancer.Ginekol Pol.2007;78(9):715-718.
[2]Parekh DJ,Ankerst DP,Troyer D,et al.Biomarkers for prostate cancer detection.J Urol.2007;178(6):2252-2259.
[3]Malyankar UM.Tumor-associated antigens and biomarkers in cancer and immune therapy.Int Rev Immunol.2007;26(3-4):223-247.
[4]Gretzer MB,Partin AW.PSA markers in prostate cancer detection.Urol Clin North Am.2003;30(4):677-686.
[5]Stephan C,Jung K,Lein M,et al.PSA and other tissue kallikreins for prostate cancer detection.Eur J Cancer.2007;43(13):1918-1926.
[6]Crawford NP,Colliver DW,Galandiuk S.Tumor markers and colorectal cancer:utility in management.J Surg Oncol.2003;84(4):239-248.
[7]Trompetas V,Panagopoulos E,Priovolou-Papaevangelou M,et al.Giant benign true cyst of the spleen with high serum level of CA 19-9.Eur J Gastroenterol Hepatol.2002;14(1):85-88.
[8]Balzano G,Di Carlo V.Is CA 19-9 useful in the management of pancreatic cancer? Lancet Oncol.2008;9(2):89-91.
[9]Nagata K,Horinouchi M,Saitou M,et al.Mucin expression profile in pancreatic cancer and the precursor lesions.J Hepatobiliary Pancreat Surg.2007;14(3):243-254.
[10]Singh PK,Wen Y,Swanson BJ,et al.Platelet-derived growth factor receptor beta-mediated phosphorylation of MUC1 enhances invasiveness in pancreatic adenocarcinoma cells.Cancer Res.2007;67(11):5201-5210.
[11]Gold DV,Karanjawala Z,Modrak DE,et al.PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma.Clin Cancer Res.2007;13(24):7380-7387.
[12]Carraway CA,Carraway KL.Sequestration and segregation of receptor kinases in epithelial cells:implications for ErbB2 oncogenesis.Sci STKE.2007;2007(381):re3.
[13]Doyle DM,Miller KD.Development of new targeted therapies for breast cancer.Cancer Treat Res.2008;141:119-134.
[14]Nesterova MV,Johnson N,Cheadle C,et al.Autoantibody cancer biomarker:extracellular protein kinase A.Cancer Res.2006;66(18):8971-8974.
[15]杜芳,王立东,齐义军,et al.食管和贲门癌及癌前病变患者血清中多个自身抗体的检测及其临床意义.中华肿瘤防治杂志.2006;13(17):1289-1292.
[16]Cho-Chung YS.Autoantibody biomarkers in the detection of cancer.Biochim Biophys Acta.2006;1762(6):587-591.
[17]Tan EM,Zhang J.Autoantibodies to tumor-associated antigens:reporters from the immune system.Immunol Rev.2008;222:328-340.
[18]吴晓江,王俞欠,季加孚.胃癌中肿瘤/睾丸抗原的表达研究及NY-ESO-1蛋白的自身抗体检测.北京大学学报(医学版).2005;37(03):252-256.
[19]Yurkovetsky ZR,Linkov FY,D EM,et al.Multiple biomarker panels for early detection of ovarian cancer.Future Oncol.2006;2(6):733-741.
[20]Finn OJ.Immune response as a biomarker for cancer detection and a lot more.N Engl J Med.2005;353(12):1288-1290.
[21]Hardouin J,Lasserre JP,Sylvius L,et al.Cancer immunomics:from serological proteome analysis to multiple affinity protein profiling.Ann N Y Acad Sci.2007;1107:223-230.
[22]Toubi E,Shoenfeld Y.Protective autoimmunity in cancer(review).Oncol Rep.2007;17(1):245-251.
[23]Cho WC,Yip TT,Ngan RK,et al.ProteinChip array profiling for identification of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma.Clin Chem.2007;53(2):241-250.
[24]Caiazzo RJ,Jr.,Tassinari OW,Ehrlich JR,et al.Autoantibody microarrays for biomarker discovery.Expert Rev Proteomics.2007;4(2):261-272.
[25]Diamond SL.Methods for mapping protease specificity.Curr Opin Chem Biol.2007;11(1):46-51.
[26]Caron M,Choquet-Kastylevsky G,Joubert-Caron R.Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics. 2007;6(7): 1115-1122.
[27] Sahin U, Tureci O, Schmitt H, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995;92(25): 11810-11813.
[28] Kuboshima M, Shimada H, Liu TL, et al. Identification of a novel SEREX antigen, SLC2A1/GLUT1, in esophageal squamous cell carcinoma. Int J Oncol. 2006;28(2):463-468.
[29] Ishikura H, Ikeda H, Abe H, et al. Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system. Int J Oncol. 2007;30(2):461-467.
[30] Mizukami M, Hanagiri T, Yasuda M, et al. Antitumor effect of antibody against a SEREX-defined antigen (UOEH-LC-1) on lung cancer xenotransplanted into severe combined immunodeficiency mice. Cancer Res. 2007;67(17):8351-8357.
[31] Hasegawa K, Koizumi F, Noguchi Y, et al. SSX expression in gynecological cancers and antibody response in patients. Cancer Immun. 2004;4:16.
[32] Kim Y, Jeoung D. Role of CAGE, a Novel Cancer/Testis Antigen, in Various Cellular Processes, Including Tumorigenesis, Cytolytic T Lymphocyte Induction, and Cell Motility. J Microbiol Biotechnol. 2008;18(3):600-610.
[33] Unwin RD, Harnden P, Pappin D, et al. Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics. 2003;3(1):45-55.
[34] Lee SY, Jeoung D. The reverse proteomics for identification of tumor antigens.J Microbiol Biotechnol. 2007;17(6):879-890.
[35] MacKeigan JP, Clements CM, Lich JD, et al. Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIalpha. Cancer Res. 2003;63(20):6928-6934.
[36] Pereira-Faca SR, Kuick R, Puravs E, et al. Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer. Cancer Res. 2007;67(24): 12000-12006.
[37] Li L, Chen SH, Yu CH, et al. Identification of hepatocellular-carcinoma-associated antigens and autoantibodies by serological proteome analysis combined with protein microarray. J Proteome Res. 2008;7(2):611-620.
[38] Jackson D, Craven RA, Hutson RC, et al. Proteomic profiling identifies afamin as a potential biomarker for ovarian cancer. Clin Cancer Res. 2007;13(24):7370-7379.
[39] Yang F, Xiao ZQ, Zhang XZ, et al. Identification of tumor antigens in human lung squamous carcinoma by serological proteome analysis. J Proteome Res. 2007;6(2):751-758.
[40] Gunawardana CG, Diamandis EP. High throughput proteomic strategies for identifying tumour-associated antigens. Cancer Lett. 2007;249(1): 110-119.
[41] Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl J Med. 2005;353(12): 1224-1235.
[42] Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. Cancer Res. 2007;67(7):3461-3467.
[43] Fernandez-Madrid F, Tang N, Alansari H, et al. Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer. Cancer Res. 2004;64(15):5089-5096.
[44] Shadidi M, Sorensen D, Dybwad A, et al. Mucosal vaccination with phage-displayed tumour antigens identified through proteomics-based strategy inhibits the growth and metastasis of 4T1 breast adenocarcinoma. Int J Oncol. 2008;32(1):241-247.
[45] Chen J, Xu XM, Underhill CB, et al. Tachyplesin activates the classic complement pathway to kill tumor cells. Cancer Res. 2005;65(11):4614-4622.
[46] Nowak JE, Chatterjee M, Mohapatra S, et al. Direct production and purification of T7 phage display cloned proteins selected and analyzed on microarrays. Biotechniques. 2006;40(2):220-227.
[47] Qiu J, Madoz-Gurpide J, Misek DE, et al. Development of natural protein microarrays for diagnosing cancer based on an antibody response to tumor antigens. J Proteome Res. 2004;3(2):261-267.
[48] Hudson ME, Pozdnyakova I, Haines K, et al. Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci U S A. 2007;104(44): 17494-17499.
[49] Madoz-Gurpide J, Kuick R, Wang H, et al. Integral protein microarrays for the identification of lung cancer antigens in sera that induce a humoral immune response.Mol Cell Proteomics.2008;7(2):268-281.
[50]Admon A,Shoshan SH.Antibodies as oncogenes:a hypothesis.Med Hypotheses.2006;67(3):471-473.
[51]Mahler V,Antoni C,Anhalt GJ,et al.Graft-versus-host-like mucocutaneous eruptions with serological features of paraneoplastic pemphigus and systemic lupus erythematosus in a patient with non-Hodgkin's lymphoma.Dermatology.1998;197(1):78-83.
[52]Kelly-Scumpia KM,Nacionales DC,Scumpia PO,et al.In vivo adjuvant activity of the RNA component of the Sm/RNP lupus autoantigen.Arthritis Rheum.2007;56(10):3379-3386.
[53]Liebes L,Potmesil M,Kim T,et al.Pharmacodynamics of topoisomerase I inhibition:Western blot determination of topoisomerase I and cleavable complex in patients with upper gastrointestinal malignancies treated with topotecan.Clin Cancer Res.1998;4(3):545-557.
[54]Al-Shukaili A,Al-Jabri AA,Al-Moundhri MS.Prognostic value of auto-antibodies in the serum of Omani patients with gastric,cancer.Saudi Med J.2006;27(12):1873-1877.
[55]Dang CV.Higher eukaryotic aminoacyl-tRNA synthetases in physiologic and pathologic states.Mol Cell Biochem.1986;71(2):107-120.
[56]Vazquez-Abad D,Carson JH,Rothfield N.Localization of histidyl-tRNA synthetase(Jo-1)in human laryngeal epithelial carcinoma cell line(HEp-2cells).Cell Tissue Res.1996;286(3):487-491.
[57]Legault D,McDermott J,Crous-Tsanaclis AM,et al.Cancer-associated myositis in the presence of anti-Jo1 autoantibodies and the antisynthetase syndrome.J Rheumatol.2008;35(1):169-171.
[58]聂轶飞,王凯娟,代丽萍,et al.肝癌相关抗原血清学自身抗体反应分析.中国公共卫生.2007;23(07):801-802.
[59]Dollinger MM,Behrens CM,Lesske J,et al.Thymostimulin in advanced hepatocellular carcinoma:a phase Ⅱ trial.BMC Cancer.2008;8(1):72.
[60]Zinkin NT,Grall F,Bhaskar K,et al.Serum proteomics,and biomarkers in hepatocellular carcinoma and chronic liver disease.Clin Cancer Res.2008;14(2):470-477.
[61]Suppiah A,Alabi A,Madden L,et al.Anti-p53 autoantibody in colorectal cancer:prognostic significance in long-term follow-up.Int J Colorectal Dis. 2008.
[62]Anderson KS,Ramachandran N,Wong J,et al.Application of Protein Microarrays for Multiplexed Detection of Antibodies to Tumor Antigens in Breast Cancer.J Proteome Res.2008;7(4):1490-1499.
[63]Chapman CJ,Murray A,McElveen JE,et al.Autoantibodies in lung cancer:possibilities for early detection and subsequent cure.Thorax.2008;63(3):228-233.
[64]刘保池,王立东,杜芳,et al.肿瘤相关抗原与自身抗体检测对食管癌早期发现和高危人群预警的意义.中华肿瘤防治杂志.2007;14(09):645-649.
[65]Nesterova M,Johnson N,Cheadle C,et al.Autoantibody biomarker opens a new gateway for cancer diagnosis.Biochim Biophys Acta.2006;1762(4):398-403.
[66]Smith RA,Cokkinides V,Eyre HJ.American Cancer Society guidelines for the early detection of cancer,2006.CA Cancer J Clin.2006;56(1):11-25;quiz 49-50.
[67]Smith RA,Cokkinides V,Eyre HJ.American Cancer Society Guidelines for the Early Detection of Cancer,2005.CA Cancer J Clin.2005;55(1):31-44;quiz 55-36.
[68]祝广峰.前列腺癌的自身抗体:针对差异表达的转录体FLJ23438和VAMP3编码抗原决定子的体液免疫应答.现代泌尿外科杂志.2007;12(01).
[69]Tomaino B,Cappello P,Capello M,et al.Autoantibody signature in human ductal pancreatic adenocarcinoma.J Proteome Res.2007;6(10):4025-4031.
[70]Agaylan A,Binder D,Sauer M,et al.A highly sensitive particle agglutination assay for the detection of P53 autoantibodies in patients with lung cancer.Cancer.2007;110(11):2502-2506.
[71]King,A.Autoantibodies as novel biomarkers for the early detection of prostate cancer.Nat Clin Pract Oncol.2006;3(1):7-8.
[72]Zhong L,Coe SP,Stromberg AJ,et al.Profiling tumor-associated antibodies for early detection of non-small cell lung cancer.J Thorac Oncol.2006;1(6):513-519.
[73]Cressey R,Pimpa S,Chewaskulyong B,et al.Simplified approaches for the development of an ELISA to detect circulating autoantibodies to p53 in cancer patients.BMC Biotechnol.2008;8:16.
[74]Fernandez Madrid F.Autoantibodies in breast cancer sera:candidate biomarkers and reporters of tumorigenesis.Cancer Lett.2005;230(2):187-198.
[75]Storr SJ,Chakrabarti J,Barnes A,et al.Use of autoantibodies in breast cancer screening and diagnosis.Expert Rev Anticancer Ther.2006;6(8):1215-1223.
[76]Lu H,Goodell V,Disis ML.Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer.J Proteome Res.2008;7(4):1388-1394.
[77]Lin HS,Talwar HS,Tarca AL,et al.Autoantibody approach for serum-based detection of head and neck cancer.Cancer Epidemiol Biomarkers Prev.2007;16(11):2396-2405.
[78]Khan S,Alvi A,Holding S,et al.The clinical significance of antinucleolar antibodies.J Clin Pathol.2008;61(3):283-286.
[79]Meffre E,Casellas R,Nussenzweig MC.Antibody regulation of B cell development.Nat Immunol.2000;1(5):379-385.
[80]Preuss KD,Zwick C,Bormann C,et al.Analysis of the B-cell repertoire against antigens expressed by human neoplasms.Immunol Rev.2002;188:43-50.
[81]Lemieux R,Bazin R.Autoantibody-induced formation of immune complexes in normal human serum.Curr Pharm Des.2006;12(2):173-179.
[82]Ehrlich JR,Tang L,Caiazzo RJ,Jr.,et al.The "Reverse Capture"Autoantibody Microarray:An Innovative Approach to Profiling the Autoantibody Response to Tissue-Derived Native Antigens.Methods Mol Biol.2008;441:175-192.
[2]姚开泰.从死因回顾调查资料看湖南省鼻咽癌流行病学的一些特点并探索其发病机理.中南大学学报(医学版).1982;7(1):10-17.
[3]黄腾波,陈德林,黄惠明,等.鼻咽癌在不同高发区人群中的发病差异.癌症.1998;17(2):84-86.
[4]Boussen H,Bouaouina N,Mokni-Baizig N,et al.Nasopharyngeal carcinoma.Recent data.Pathol Biol(Paris).2005;53(1):45-51.
[5]Chan AT,Teo PM,Johnson PJ.Nasopharyngeal carcinoma.Ann Oncol.2002;13(7):1007-1015.
[6]Yu MC,Yuan JM.Epidemiology of nasopharyngeal carcinoma.Semin Cancer Biol.2002;12(6):421-429.
[7]Chan AT,Teo PM,Huang DP.Pathogenesis and treatment of nasopharyngeal carcinoma.Semin Oncol.2004;31(6):794-801.
[8]Lin JC,Wang WY,Chen KY,et al.Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma.N Engl J Med.2004;350(24):2461-2470.
[9]Marcy PY,Zhu Y,Bensadoun RJ.Target volumes in radiotherapy - head and neck tumors intensity-modulated radiation therapy(IMRT)of nasopharyngeal carcinoma:practical aspects in the delineation of target volumes and organs at risk.Cancer Radiother.2005;9(4):240-250.
[10]Lee N,Puri DR,Blanco A.I,et al.Intensity-modulated radiation therapy in head and neck cancers:an update.Head Neck.2007;29(4):387-400.
[11]Ma BB,Chan AT.Recent perspectives in the role of chemotherapy in the management of advanced nasopharyngeal carcinoma.Cancer.2005;103(1):22-31.
[12]Chan AT,Teo PM,Leung TW,et al.The role of chemotherapy in the management of nasopharyngeal carcinoma.Cancer.1998;82(6):1003-1012.
[13]Chong VF.Tumour volume measurement in head and neck cancer.Cancer Imaging.2007;7 Spec No A:S47-49.
[14]Jeyakumar A,Brickman TM,Jeyakumar A,et al.Review of nasopharyngeal carcinoma. Ear Nose Throat J. 2006;85(3):168-170,172-163,184.
[15] Kristensen CA, Specht LK. Combined chemotherapy and radiotherapy in patients with nasopharyngeal cancer. A survey of a Cochrane review. Ugeskr Laeger. 2008;170(6):430-433.
[16] O'Sullivan B. Nasopharynx cancer: therapeutic value of chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2007;69(2 Suppl):S118-121.
[17] King AD, Ma BB, Yau YY, et al. The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis. Br J Radiol. 2008;81(964):291-298.
[18] Cho WC. Nasopharyngeal carcinoma: molecular biomarker discovery and progress. Mol Cancer. 2007;6:1.
[19] Caron M, Choquet-Kastylevsky G, Joubert-Caron R. Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics. 2007;6(7):1115-1122.
[20] Toubi E, Shoenfeld Y. Protective autoimmunity in cancer (review). Oncol Rep. 2007;17(1):245-251.
[21] Tiwawech D, Srivatanakul P, Karalak A, et al. Cytochrome P450 2A6 polymorphism in nasopharyngeal carcinoma. Cancer Lett. 2006;241(1):135- 141.
[22] Jiang JH, Li Z, Su G, et al. [Study on genetic polymorphisms of CYP2F1 gene in Guangdong population of China]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2006;23(4):383-387.
[23] Cao Y, Miao XP, Huang MY, et al. Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population. BMC Cancer. 2006;6:167.
[24] Catarino RJ, Breda E, Coelho V, et al. Association of the A870G cyclin D1 gene polymorphism with genetic susceptibility to nasopharyngeal carcinoma. Head Neck. 2006;28(7):603-608.
[25] Xiao B, Fan S, Zeng Z, et al. Purification of novel UBAP1 protein and its decreased expression on nasopharyngeal carcinoma tissue microarray. Protein Expr Purif. 2006;47(1):60-67.
[26] Chow LS, Lam CW, Chan SY, et al. Identification of RASSF1A modulated genes in nasopharyngeal carcinoma. Oncogene. 2006;25(2):310-316.
[27] Lo PH, Xie D, Chan KC, et al. Reduced expression of RASSF1A in esophag -eal and nasopharyngeal carcinomas significantly correlates with tumor stage. Cancer Lett. 2007;257(2): 199-205.
[28] Soejima H, Kawamoto S, Akai J, et al. Isolation of novel heart-specific genes using the BodyMap database. Genomics. 2001;74(1): 115-120.
[29] Zhang SQ, Peng H, Song LY, et al. Detection of KIAA1173 gene expression in nasopharyngeal carcinoma tissues and cell lines on tissue microarray. Ai Zheng. 2005;24(11): 1322-1326.
[30] Sun D, Zhang Z, Van do N, et al. Aberrant methylation of CDH13 gene in nasopharyngeal carcinoma could serve as a potential diagnostic biomarker. Oral Oncol. 2007;43(1):82-87.
[31] Wu CC, Chien KY, Tsang NM, et al. Cancer cell-secreted proteomes as a basis for searching potential tumor markers: nasopharyngeal carcinoma as a model. Proteomics. 2005;5(12):3173-3182.
[32] Wong BC, Chan KC, Chan AT, et al. Reduced plasma RNA integrity in nasopharyngeal carcinoma patients. Clin Cancer Res. 2006; 12(8):2512-2516.
[33] Lung HL, Bangarusamy DK, Xie D, et al. THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma. Oncogene. 2005;24(43):6525-6532.
[34]. Yau WL, Lung HL, Zabarovsky ER, et al. Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma. Int J Cancer. 2006; 119(12):2821-2826.
[35] Peng D, Ren CP, Yi HM, et al. Genetic and epigenetic alterations of DLC-1, a candidate tumor suppressor gene, in nasopharyngeal carcinoma. Acta Biochim Biophys Sin (Shanghai). 2006;38(5):349-355.
[36] Qiu GH, Tan LK, Loh KS, et al. The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene. 2004;23(27):4793-4806.
[37]. Ying J, Srivastava G, Hsieh WS, et al. The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors. Clin Cancer Res. 2005; 11(18):6442-6449.
[38] Geara FB, Sanguineti G, Tucker SL, et al. Carcinoma of the nasopharynx treated by radiotherapy alone:determinants of distant metastasis and survival.Radiother Oncol.1997;43(1):53-61.
[39]Shi X,Yuan X,Tao D,et al.Analysis of DNA ploidy,cell cycle and Ki67antigen in nasopharyngeal carcinoma by flow cytometry.J Huazhong Univ Sci Technolog Med Sci.2005;25(2):198-201.
[40]Zhao GQ,Xu Y,Wang Q.Significance of serum vascular endothelial growth factor test before radiotherapy in patients with nasopharyngeal carcinoma.Zhong Xi Yi Jie He Xue Bao.2005;3(4):274-277.
[41]Cho WC,Yip TT,Yip C,et al.Identification of serum amyloid a protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling.Clin Cancer Res.2004;10(1 Pt 1):43-52.
[42]Cho WC,Yip TT,Ngan RK,et al.ProteinChip array profiling for identific -ation of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma.Clin Chem.2007;53(2):241-250.
[43]Minard ME,Kim LS,Price JE,et al..The role of the guanine nucleotide exchange factor Tiaml in cellular migration,invasion,adhesion and tumor progression.Breast Cancer Res Treat.2004;84(1):21-32.
[44]Mo L,Wang H,Huang G,et al.Correlation between expression of the Tiaml gene and the invasion and metastasis in nasopharyngeal carcinoma.Lin Chuang Er Bi Yan Hou Ke Za Zhi.2005;19(17):785-787.
[45]Horikawa T,Kaizaki Y,Kato H,et al.Expression of interleukin-8 receptor A predicts poor outcome in patients with nasopharyngeal carcinoma.Laryngoscope.2005;115(1):62-67.
[46]Tee YT,Chen GD,Lin LY,et al.Nm23-H1:a metastasis-associated gene.Taiwan J Obstet Gynecol.2006;45(2):107-113.
[47]Jiang WZ,Liao YP,Zhao SP,et al.Expression clinical significance of nm23-H1 and vessel endothelium growth factor protein in nasopharyngeal carcinoma.Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi.2006;41(3):200-204.
[48]Tsang CW,Lin X,Gudgeon NH,et al.CD4+ T-cell responses to Epstein-Barr virus nuclear antigen EBNA1 in Chinese populations are highly focused on novel C-terminal domain-derived epitopes.J Virol.2006;80(16):8263-8266.
[49]Fachiroh J,Paramita DK,Hariwiyanto B,et al.Single-assay combination of Epstein-Barr Virus(EBV)EBNA1-and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G(IgG)and IgA antibody levels in sera from nasopharyngeal carcinoma patients:options for field screening.J Clin Microbiol.2006;44(4):1459-1467.
[50]Tarbouriech N,Ruggiero F,de Turenne-Tessier M,et al.Structure of the Epstein-Barr virus oncogene BARF1.J Mol Biol.2006;359(3):667-678.
[51]Swissa M,Amital-Teplizki H,Haim N,et al.Autoantibodies in neoplasia.An unresolved enigma.Cancer.1990;65(11):2554-2558.
[52]Bidoli E,Villalta D,Battistin M,et al.Epidemiological and ethical aspects of multiplex autoantibody testing.Autoimmun Rev.2007;6(6):354-358.
[53]Amos MD,Bridges AJ.Standards for autoantibody testing;addressing future needs for autoimmune disease and cancer diagnosis.Cancer Biomark.2005;1(4-5):221-227.
[54]Cho-Chung YS.Autoantibody biomarkers in the detection of cancer.Biochim Biophys Acta.2006;1762(6):587-591.
[55]Finn OJ.Immune response as a biomarker for cancer detection and a lot more.N Engl J Med.2005;353(12):1288-1290.
[56]Tan EM.Autoantibodies as reporters identifying aberrant cellular mechanisms in tumorigenesis.J Clin Invest.2001;108(10):1411-1415.
[57]Admon A,Shoshan SH.Antibodies as oncogenes:a hypothesis.Med Hypotheses.2006;67(3):471-473.
[58]Sahin U,Tureci O,Schmitt H,et al.Human neoplasms elicit multiple specific immune responses in the autologous host.Proc Natl Acad Sci U S A.1995;92(25):11810-11813.
[59]Lee SY,Obata Y,Yoshida M,et al.Immunomic analysis of human sarcoma.Proc Natl Acad Sci U S A.2003;100(5):2651-2656.
[60]Preuss KD,Zwick C,Bormann C,et al.Analysis of the B-cell repertoire against antigens expressed by human neoplasms.Immunol Rev.2002;188:43-50.
[61]Nesterova M,Johnson N,Cheadle C,et al.Autoantibody biomarker opens a new gateway for cancer diagnosis.Biochim Biophys Acta.2006;1762(4):398-403.
[62]Lennon VA,Kryzer TJ,Griesmann GE,et al.Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes.N Engl J Med.1995;332(22):1467-1474.
[63]Spuler S,Sarropoulos A,Marx A,et al.Thymoma-associated myasthenia gravis.Transplantation of thymoma and extrathymomal thymic tissue into SCID mice.Am J Pathol.1996;148(5):1359-1365.
[64]Gordon PA,Baylis PH,Bird GW.Tumour-induced autoimmune haemolytic anaemia.Br Med J.1976;1(6025):1569-1570.
[65]Bellone JD,Kunicki TJ,Aster RH.Immune thrombocytopenia associated with carcinoma.Ann Intern Med.1983;99(4):470-472.
[66]Kruskall MS,Weitzman SA,Stossel TP,et al.Lymphoma with autoimmune neutropenia and hepatic sinusoidal infiltration:a syndrome.Ann Intern Med.1982;97(2):202-205.
[67]Fishman P,Merimski O,Baharav E,et al.Autoantibodies to tyrosinase:the bridge between melanoma and vitiligo.Cancer.1997;79(8):1461-1464.
[68]Sigurgeirsson B,Lindelof B,Edhag O,et al.Risk of cancer in patients with dermatomyositis or polymyositis.A population-based study.N Engl J Med.1992;326(6):363-367.
[69]Kinlen LJ.Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment.Am J Med.1985;78(1A):44-49.
[70]Bematsky S,Clarke A,Ramsey-Goldman R.Malignancy and systemic lupus erythematosus.Curr Rheumatol Rep.2002;4(4):351-358.
[71]Ruiz-Irastorza G,Ugarte A,Egurbide MV,et al.Antimalarials may influence the risk of malignancy in systemic lupus erythematosus.Ann Rheum Dis.2007;66(6):815-817.
[72]Abu-Shakra M,Gladman DD,Urowitz MB.Malignancy in systemic lupus erythematosus.Arthritis Rheum.1996;39(6):1050-1054.
[73]Tzioufas AG,Boumba DS,Skopouli FN,et al.Mixed monoclonal cryoglobu -linemia and monoclonal rheumatoid factor cross-reactive idiotypes as predictive factors for the development of lymphoma in primary Sjogren's syndrome.Arthritis Rheum.1996;39(5):767-772.
[74]Zatuchni J,Campbell WN,Zarafonetis CJ.Pulmonary fibrosis and terminal bronchiolar(alveolar-cell)carcinoma in scleroderma.Cancer.1953;6(6):1147-1158.
[75]Okayasu I,Fujiwara M,Hara Y,et al.Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma.A study of surgical cases among Japanese,and white and African Americans.Cancer.1995;76(11):2312-2318.
[76]Swissa M,Cohen Y,Shoenfeld Y.Autoantibodies in the sera of patients with lymphoma.Leuk Lymphoma.1992;7(1-2):117-122.
[77]Thomas PJ,Kaur JS,Aitcheson CT,et al.Antinuclear,antinucleolar,and anticytoplasmic antibodies in patients with malignant melanoma.Cancer Res.1983;43(3):1372-1380.
[78]Twomey JJ,Rossen RD,Lewis VM,et al.Rheumatoid factor and tumor-host interaction.Proc Natl Acad Sci U S A.1976;73(6):2106-2108.
[79]Manz RA,Hauser AE,Hiepe F,et al.Maintenance of serum antibody levels.Annu Rev Immunol.2005;23:367-386.
[80]Hamano Y,Tsukamoto K,Abe M,et al.Genetic dissection of vasculitis,myeloperoxidase-specific antineutrophil cytoplasmic autoantibody production,and related traits in spontaneous crescentic glomerulonephritis-forming/Kinjoh mice.J Immunol.2006;176(6):3662-3673.
[81]Lemieux R,Bazin R.Autoantibody-induced formation of immune complexes in normal human serum.Curr Pharm Des.2006;12(2):173-179.
[82]Plotz PH.The autoantibody repertoire:searching for order.Nat Rev Immunol.2003;3(1):73-78.
[83]Wardemann H,Yurasov S,Schaefer A,et al.Predominant autoantibody production by early human B cell precursors.Science.2003;301(5638):1374-1377.
[84]Gay D,Saunders T,Camper S,et al.Receptor editing:an approach by autoreactive B cells to escape tolerance.J Exp Med.1993;177(4):999-1008.
[85]Tiegs SL,Russell DM,Nemazee D.Receptor editing in self-reactive bone marrow B cells.J Exp Med.1993;177(4):1009-1020.
[86]Goodnow CC,Crosbie J,Adelstein S,et al.Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice.Nature.1988;334(6184):676-682.
[87]Nemazee DA,Burki K.Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class Ⅰ antibody genes.Nature.1989;337(6207):562-566.
[88]Tiller T,Tsuiji M,Yurasov S,et al.Autoreactivity in human IgG+ memory B cells.Immunity.2007;26(2):205-213.
[89]Ding C,Yan J.Regulation of autoreactive B cells:checkpoints and activation.Arch Immunol Ther Exp(Warsz).2007;55(2):83-89.
[90] Etzioni R, Urban N, Ramsey S, et al. The case for early detection. Nat Rev Cancer. 2003;3(4):243-252.
[91] Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2006. CA Cancer J Clin. 2006;56(1):11-25; quiz 49-50.
[92] Chen YT, Gure AO, Tsang S, et al. Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library. Proc Natl Acad Sci U S A. 1998;95(12):6919-6923.
[93] Scanlan MJ, Gure AO, Jungbluth AA, et al. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev. 2002; 188:22-32.
[94] Scanlan MJ, Welt S, Gordon CM, et al. Cancer-related serological recognition of human colon cancer: identification of potential diagnostic and immunotherapeutic targets. Cancer Res. 2002;62(14):4041-4047.
[95] Schmitz-Winnenthal FH, Galindo-Escobedo LV, Rimoldi D, et al. Potential target antigens for immunotherapy in human pancreatic cancer. Cancer Lett. 2007;252(2):290-298.
[96] Seliger B, Kellner R. Design of proteome-based studies in combination with serology for the identification of biomarkers and novel targets. Proteomics. 2002;2(12): 1641-1651.
[97] Naour FL, Brichory F, Beretta L, et al. Identification of tumor-associated antigens using proteomics. Technol Cancer Res Treat. 2002;1(4):257-262.
[98] Hardouin J, Lasserre JP, Sylvius L, et al. Cancer immunomics: from serological proteome analysis to multiple affinity protein profiling. Ann N Y Acad Sci. 2007; 1107:223-230.
[99] Le Naour F, Misek DE, Krause MC, et al. Proteomics-based identification of RS/DJ-1 as a novel circulating tumor antigen in breast cancer. Clin Cancer Res. 2001;7(11):3328-3335.
[100] Sarkissian G, Fergelot P, Lamy PJ, et al. Identification of Pro-MMP-7 as a Serum Marker for Renal Cell Carcinoma by Use of Proteomic Analysis. Clin Chem.2008;54(3):574-581.
[101] Unwin RD, Harnden P, Pappin D, et al. Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics. 2003;3(1):45-55.
[102] Prasannan L, Misek DE, Hinderer R, et al. Identification of beta-tubulin isoforms as tumor antigens in neuroblastoma. Clin Cancer Res. 2000;6(10): 3949-3956.
[103] Klade CS, Voss T, Krystek E, et al. Identification of tumor antigens in renal cell carcinoma by serological proteome analysis. Proteomics. 2001;l(7):890- 898.
[104] Lichtenfels R, Kellner R, Atkins D, et al. Identification of metabolic enzymes in renal cell carcinoma utilizing PROTEOMEX analyses. Biochim Biophys Acta.2003;1646(1-2):21-31.
[105] Seliger B, Menig M, Lichtenfels R, et al. Identification of markers for the selection of patients undergoing renal cell carcinoma-specific immunotherapy. Proteomics. 2003;3(6):979-990.
[106] Huang Y, Franklin J, Gifford K, et al. A high-throughput proteo-genomics method to identify antibody targets associated with malignant disease. Clin Immunol. 2004;111(2):202-209.
[107] Velculescu VE, Zhang L, Vogelstein B, et al. Serial analysis of gene expression. Science. 1995;270(5235):484-487.
[108] Caron M, Joubert-Caron R, Canelle L, et al. Serological Proteome Analysis (SERPA) and Multiple Affinity Protein Profiling (MAPPING) to Discover Cancer Biomarkers. Mol Cell Proteomics. 2005;4(8):s142.
[109] Hardouin J, Duchateau M, Canelle L, et al. Thiophilic adsorption revisited. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;845(2):226-231.
[110] Yin H, Killeen K, Brennen R, et al. Microfluidic chip for peptide analysis with an integrated HPLC column, sample enrichment column, and nanoelectrospraytip. Anal Chem. 2005;77(2):527-533.
[111] Brennen RA, Yin H, Killeen KP. Microfluidic gradient formation for nanoflow chip LC. Anal Chem. 2007;79(24):9302-9309.
[112] Chen YT. Cancer vaccine: identification of human tumor antigens by SEREX. Cancer J. 2000;6 Suppl 3:S208-217.
[113] Jager D. Potential target antigens for immunotherapy identified by serological expression cloning (SEREX). Methods Mol Biol. 2007;360:319-326.
[114] Jalbout M, Bel Hadj Jrad B, Bouaouina N, et al. Autoantibodies to tubulin are specifically associated with the young age onset of the nasopharyngeal carcinoma. Int J Cancer. 2002;101(2): 146-150.
[115] Lamelin JP, de-The G, Revillard JP, et al. Autoantibodies (cold lymphocy-totoxins, antiactin antibodies and antinuclear factors) in nasopharyngeal carcinoma patients. IARC Sci Publ. 1978(20):523-536.
[116] Henle W, Henle G, Lanier AP, et al. Attachment of antinuclear antibodies to nasopharyngeal carcinoma or other cells during preparation of biopsy imprints. J Natl Cancer Inst. 1986;76(6): 1041-1046.
[117] Takimoto T, Ishikawa S, Masuda K, et al. Antinuclear antibodies in the sera of patients with nasopharyngeal carcinoma. Am J Otolaryngol. 1989;10(6):399- 403.
[118] Bel Hadj Jrad B, Mahfouth W, Bouaouina N, et al. A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction. Cancer Lett. 2006;233(1):21-27.
[119] Sapir T, Blank M, Shoenfeld Y. Immunomodulatory effects of intravenous immunoglqbulins as a treatment for autoimmune diseases, cancer, and recurrent pregnancy loss. Ann N Y Acad Sci. 2005;1051:743-778.
[120] Fernandez Madrid F. Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis. Cancer Lett. 2005;230(2): 187-198.
[121] Himoto T, Kuriyama S, Zhang JY, et al. Analyses of autoantibodies against tumor-associated antigens in patients with hepatocellular carcinoma. Int J Oncol. 2005;27(4): 1079-1085.
[122] Conry RM, Allen KO, Lee S, et al. Human autoantibodies to carcinoe -mbryonic antigen (CEA) induced by a vaccinia-CEA vaccine. Clin Cancer Res.2000;6(1):34-41.
[123] Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl J Med. 2005;353(12): 1224-1235.
[124] King, A. Autoantibodies as novel biomarkers for the early detection of prostate cancer. Nat Clin Pract Oncol. 2006;3(1):7-8.
[125] Carlizzi G, Ciarla MV, Di Luzio A, et al. Autoantibodies in patients with monoclonal gammopathies. Ann N Y Acad Sci. 2007; 1107:206-211.
[126] Marchalonis JJ, Schluter SF, Sepulveda RT, et al. Immunomodulation by immunopeptides and autoantibodies in aging, autoimmunity, and infection. Ann N Y Acad Sci. 2005; 1057:247-259.
[127] Kutok JL, Wang F. Spectrum of Epstein-Barr virus-associated diseases. Annu Rev Pathol. 2006; 1:375-404.
[128] Hecht JL, Aster JC. Molecular biology of Burkitt's lymphoma. J Clin Oncol. 2000;18(21):3707-3721.
[129] Imai S, Koizumi S, Sugiura M, et al. Gastric carcinoma: monoclonal epithelial malignant cells expressing Epstein-Barr virus latent infection protein. Proc Natl Acad Sci U S A. 1994;91(19):9131-9135.
[130] Sugiura M, Imai S, Tokunaga M, et al. Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. Br J Cancer. 1996;74(4):625-631.
[131] McClain KL, Leach CT, Jenson HB, et al. Association of Epstein-Barr virus with leiomyosarcomas in children with AIDS. N Engl J Med. 1995;332(1):12-18.
[132] Chang Y, Cheng SD, Tsai CH. Chromosomal integration of Epstein-Barr virus genomes in nasopharyngeal carcinoma cells. Head Neck. 2002;24(2): 143-150.
[133] Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228(4705):1315-1317.
[134] Jimenez J, Santisteban A, Carazo JM, et al. Computer graphic display method for visualizing three-dimensional biological structures. Science. 1986;232 (4754):1113-1115.
[135] Gershoni JM, Roitburd-Berman A, Siman-Tov DD, et al. Epitope mapping: the first step in developing epitope-based vaccines. BioDrugs. 2007;21(3):145- 156.
[136] Sidhu SS, Koide S. Phage display for engineering and analyzing protein interaction interfaces. Curr Opin Struct Biol. 2007; 17(4) :481-487.
[137] Scheuermann J, Dumelin CE, Melkko S, et al. DNA-encoded chemical libraries. J Biotechnol. 2006;126(4):568-581.
[138] Diamond SL. Methods for mapping protease specificity. Curr Opin Chem Biol. 2007;11(1):46-51.
[139] Sergeeva A, Kolonin MG, Molldrem JJ, et al. Display technologies: application for the discovery of drug and gene delivery agents. Adv Drug Deliv Rev. 2006;58(15): 1622-1654.
[140] Kehoe JW, Kay BK. Filamentous phage display in the new millennium. Chem Rev. 2005;105(11):4056-4072.
[141] Hoess RH. Bacteriophage lambda as a vehicle for peptide and protein display. Cun Pharm Biotechnol. 2002;3(1):23-28.
[142] Shivachandra SB, Li Q, Peachman KK, et al. Multicomponent anthrax toxin display and delivery using bacteriophage T4. Vaccine. 2007;25(7): 1225-1235.
[143] Cerritelli ME, Conway JF, Cheng N, et al. Molecular mechanisms in bacteriophage T7 procapsid assembly, maturation, and DNA containment. Adv Protein Chem. 2003 ;64:301-323.
[144] Kalnina Z, Silina K, Meistere I, et al. Evaluation of T7 and lambda phage display systems for survey of autoantibody profiles in cancer patients. J Immunol Methods. 2008. (in print)
[145] Chen J, Xu XM, Underhill CB, et al. Tachyplesin activates the classic complement pathway to kill tumor cells. Cancer Res. 2005;65(11):4614-4622.
[146] Nowak JE, Chatterjee M, Mohapatra S, et al. Direct production and purification of T7 phage display cloned proteins selected and analyzed on microarrays. Biotechniques. 2006;40(2):220-227.
[147] Roman I, Figys J, Steurs G, et al. Direct measurement of VDAC-actin interaction by surface plasmon resonance. Biochim Biophys Acta. 2006; 1758(4):479-486.
[148] Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. Cancer Res. 2007; 67(7):3461-3467.
[149] Sheu TJ, Schwarz EM, Martinez DA, et al. A phage display technique identifies a novel regulator of cell differentiation. J Biol Chem. 2003;278(1): 438-443.
[150] Zhong L, Peng X, Hidalgo GE, et al. Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients. Cancer Detect Prev. 2003;27(4):285-290.
[151] Conroy SE, Sasieni PD, Fentiman I, et al. Autoantibodies to the 90kDa heat shock protein and poor survival in breast cancer patients. Eur J Cancer. 1998;34(6):942-943.
[152] Trieb K, Gerth R, Windhager R, et al. Serum antibodies against the heat shock protein 60 are elevated in patients with osteosarcoma. Immunobiology. 2000;201(3-4):368-376.
[153] Trieb K, Gerth R, Holzer G, et al. Antibodies to heat shock protein 90 in osteosarcoma patients correlate with response to neoadjuvant chemotherapy. Br J Cancer. 2000;82(1):85-87.
[154] Fujita Y, Nakanishi T, Miyamoto Y, et al. Proteomics-based identification of autoantibody against heat shock protein 70 as a diagnostic marker in esophageal squamous cell carcinoma. Cancer Lett. 2008.(in print)
[155] Conroy SE, Sasieni PD, Amin V, et al. Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer. Br J Cancer. 1998;77(11):1875-1879.
[156] Stockert E, Jager E, Chen YT, et al. A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med. 1998;187(8): 1349-1354.
[157] Fernandez-Madrid F, Tang N, Alansari H, et al. Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer. Cancer Res. 2004;64(15):5089-5096.
[158] Pelucchi A, Ciceri E, Clementi F, et al. Calcium channel autoantibodies in myasthenic syndrome and small cell lung cancer. Am Rev Respir Dis. 1993; 147(5): 1229-1232.
[159] Lang B, Evoli A. SOX1 autoantibodies: tumor markers in LEMS patients? Neurology. 2008;70( 12):906-907.
[160] Rennert G Prevention and early detection of colorectal cancer—new horizons. Recent Results Cancer Res. 2007;174:179-187.
[161] Karakiewicz PI, Perrotte P, McCormack M, et al. Early detection of prostate cancer with ultrasound-guided systematic needle biopsy. Can J Urol. 2005; 12 Suppl 2:5-8.
[162] Vlastos G, Verkooijen HM. Minimally invasive approaches for diagnosis and treatment of early-stage breast cancer. Oncologist. 2007;12(1):1-10.
[163] Cassidy A, Duffy SW, Myles JP, et al. Lung cancer risk prediction: a tool for early detection. Int J Cancer. 2007;120(1):1-6.
[164] Sasco AJ. Screening of undifferentiated carcinoma of the nasopharynx. Bull Cancer. 1996;83(5):344-351.
[165] Taweevisit M. Overexpression of p53 and neoplastic cell proliferation in undifferentiated nasopharyngeal carcinoma. Southeast Asian J Trop Med Public Health. 2007;38(1): 136-140.
[166] Chan KC, Lo YM. Clinical applications of plasma Epstein-Barr virus DNA analysis and protocols for the quantitative analysis of the size of circulating Epstein-Barr virus DNA.Methods Mol Biol.2006;336:111-121.
[167]Heinzelmann-Schwarz VA,Gardiner-Garden M,Henshall SM,et al.Overexpression of the cell adhesion molecules DDR1,Claudin 3,and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer.Clin Cancer Res.2004;I0(13):4427-4436.
[168]Huddleston HG,Wong KK,Welch WR,et al.Clinical applications of microarray technology:creatine kinase B is an up-regulated gene in epithelial ovarian cancer and shows promise as a serum marker.Gynecol Oncol.2005;96(1):77-83.
[169]Bachelot T,Ratel D,Menetrier-Caux C,et al.Autoantibodies to endostatin in patients with breast cancer:correlation to endostatin levels and clinical outcome.Br J Cancer.2006;94(7):1066-1070.
[170]Hanahan D,Weinberg RA.The hallmarks of cancer.Cell.2000;100(1):57-70.
[171]Song LB,Zeng MS,Liao WT,et al.Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells.Cancer Res.2006;66(12):6225-6232.
[172]Ma BB,Leungrn SF,Hui EP,et al.Prospective validation of serum CYFRA 21-1,beta-2-microglobulin,and ferritin levels as prognostic markers in patients with nonmetastatic nasopharyngeal carcinoma undergoing radiotherapy.Cancer.2004;101(4):776-781.
[173]Ho DW,Yang ZF,Wong BY,et al.Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry serum protein profiling to identify nasopharyngeal carcinoma.Cancer.2006;107(1):99-107.
[174]Emoto K,Yamada Y,Sawada H,et al.Annexin Ⅱ overexpression correlates with stromal tenascin-C overexpression:a prognostic marker in colorectal carcinoma.Cancer.2001;92(6):1419-1426.
[175]Lee KD,Lee HH,Joo HB,et al.Expression of MAGE A 1-6 mRNA in sputa of head and neck cancer patients—a preliminary report.Anticancer Res.2006;26(2B):1513-1518.
[176]Mambula SS,Calderwood SK.Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes.J Immunol.2006;177(11):7849-7857.
[177]Liu R,Wang X,Chen GY,et al.The prognostic role of a gene signature from tumorigenic breast-cancer cells.N Engl J Med.2007;356(3):217-226.
[178] Adams JM, Cory S. Oncogene co-operation in leukaemogenesis. Cancer Surv. 1992;15:119-141.
[179] Liebermann DA, Hoffman B. Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation. Stem Cells. 1994;12(4):352-369.
[180] Gorrini C, Squatrito M, Luise C, et al. Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature. 2007;448(7157): 1063-1067.
[181] Raaphorst FM. Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1. Trends Immunol. 2003;24(10):522-524.
[182] Liu S, Dontu G, Wicha MS. Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 2005;7(3):86-95.
[183] van Lohuizen M, Verbeek S, Scheijen B, et al. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991;65(5):737-752.
[184] Haupt Y, Alexander WS, Barri G, et al. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991;65(5):753-763.
[185] van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999- 2009.
[186] Mihara K, Chowdhury M, Nakaju N, et al. Bmi-1 is useful as a novel molecular marker for predicting progression of myelodysplastic syndrome and patient prognosis. Blood. 2006;107(1):305-308.
[187] Breuer RH, Snijders PJ, Sutedja GT, et al. Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions. Lung Cancer. 2005;48(3):299-306.
[188] Merkerova M, Bruchova H, Kracmarova A, et al. Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia transformation. Leuk Lymphoma. 2007;48(4):793-801.
[189] Yoshizaki T, Wakisaka N, Kondo S, et al. Treatment of locally recurrent epstein-barr virus-associated nasopharyngeal carcinoma using the anti-viral agent cidofovir.J Med Virol.2008;80(5):879-882.
[190]Seto E,Ooka T,Middeldorp J,et al.Reconstitution of nasopharyngeal carcinoma-type EBV infection induces tumorigenicity.Cancer Res.2008;68(4):1030-1036.
[191]Pathmanathan R,Prasad U,Chandrika G,et al.Undifferentiated,nonkeratiniz -ing,and squamous cell carcinoma of the nasopharynx.Variants of Epstein-Barr virus-infected neoplasia.Am J Pathol.1995;146(6):1355-1367.
[192]Tam JS,Murray HG.Nasopharyngeal carcinoma and Epstein-Barr virus associated serologic markers.Ear Nose Throat J.1990;69(4):261-267.
[193]Deyrup AT.Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.Hum Pathol.2008;39(4):473-483.
[194]Buccheri GF,Violante B,Sartoris AM,et al.Clinical value of a multiple biomarker assay in patients with bronchogenic carcinoma.Cancer.1986;57(12):2389-2396.
[195]Buccheri G,Ferrigno D.Serum biomarkers of non-neuron-endocrine origin in small-cell lung cancer:a 16-year study on carcinoembryonic antigen,tissue polypeptide antigen and lactate dehydrogenase.Lung Cancer.2000;30(1):37-49.
[196]Pectasides D,Bafaloucos D,Antoniou F,et al.TPA,TATI,CEA,AFP,beta-HCG,PSA,SCC,and CA 19-9 for monitoring transitional cell carcinoma of the bladder.Am J Clin Oncol.1996;19(3):271-277.
[1]Markowska J.Tumor makrers in cervical cancer.Ginekol Pol.2007;78(9):715-718.
[2]Parekh DJ,Ankerst DP,Troyer D,et al.Biomarkers for prostate cancer detection.J Urol.2007;178(6):2252-2259.
[3]Malyankar UM.Tumor-associated antigens and biomarkers in cancer and immune therapy.Int Rev Immunol.2007;26(3-4):223-247.
[4]Gretzer MB,Partin AW.PSA markers in prostate cancer detection.Urol Clin North Am.2003;30(4):677-686.
[5]Stephan C,Jung K,Lein M,et al.PSA and other tissue kallikreins for prostate cancer detection.Eur J Cancer.2007;43(13):1918-1926.
[6]Crawford NP,Colliver DW,Galandiuk S.Tumor markers and colorectal cancer:utility in management.J Surg Oncol.2003;84(4):239-248.
[7]Trompetas V,Panagopoulos E,Priovolou-Papaevangelou M,et al.Giant benign true cyst of the spleen with high serum level of CA 19-9.Eur J Gastroenterol Hepatol.2002;14(1):85-88.
[8]Balzano G,Di Carlo V.Is CA 19-9 useful in the management of pancreatic cancer? Lancet Oncol.2008;9(2):89-91.
[9]Nagata K,Horinouchi M,Saitou M,et al.Mucin expression profile in pancreatic cancer and the precursor lesions.J Hepatobiliary Pancreat Surg.2007;14(3):243-254.
[10]Singh PK,Wen Y,Swanson BJ,et al.Platelet-derived growth factor receptor beta-mediated phosphorylation of MUC1 enhances invasiveness in pancreatic adenocarcinoma cells.Cancer Res.2007;67(11):5201-5210.
[11]Gold DV,Karanjawala Z,Modrak DE,et al.PAM4-reactive MUC1 is a biomarker for early pancreatic adenocarcinoma.Clin Cancer Res.2007;13(24):7380-7387.
[12]Carraway CA,Carraway KL.Sequestration and segregation of receptor kinases in epithelial cells:implications for ErbB2 oncogenesis.Sci STKE.2007;2007(381):re3.
[13]Doyle DM,Miller KD.Development of new targeted therapies for breast cancer.Cancer Treat Res.2008;141:119-134.
[14]Nesterova MV,Johnson N,Cheadle C,et al.Autoantibody cancer biomarker:extracellular protein kinase A.Cancer Res.2006;66(18):8971-8974.
[15]杜芳,王立东,齐义军,et al.食管和贲门癌及癌前病变患者血清中多个自身抗体的检测及其临床意义.中华肿瘤防治杂志.2006;13(17):1289-1292.
[16]Cho-Chung YS.Autoantibody biomarkers in the detection of cancer.Biochim Biophys Acta.2006;1762(6):587-591.
[17]Tan EM,Zhang J.Autoantibodies to tumor-associated antigens:reporters from the immune system.Immunol Rev.2008;222:328-340.
[18]吴晓江,王俞欠,季加孚.胃癌中肿瘤/睾丸抗原的表达研究及NY-ESO-1蛋白的自身抗体检测.北京大学学报(医学版).2005;37(03):252-256.
[19]Yurkovetsky ZR,Linkov FY,D EM,et al.Multiple biomarker panels for early detection of ovarian cancer.Future Oncol.2006;2(6):733-741.
[20]Finn OJ.Immune response as a biomarker for cancer detection and a lot more.N Engl J Med.2005;353(12):1288-1290.
[21]Hardouin J,Lasserre JP,Sylvius L,et al.Cancer immunomics:from serological proteome analysis to multiple affinity protein profiling.Ann N Y Acad Sci.2007;1107:223-230.
[22]Toubi E,Shoenfeld Y.Protective autoimmunity in cancer(review).Oncol Rep.2007;17(1):245-251.
[23]Cho WC,Yip TT,Ngan RK,et al.ProteinChip array profiling for identification of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma.Clin Chem.2007;53(2):241-250.
[24]Caiazzo RJ,Jr.,Tassinari OW,Ehrlich JR,et al.Autoantibody microarrays for biomarker discovery.Expert Rev Proteomics.2007;4(2):261-272.
[25]Diamond SL.Methods for mapping protease specificity.Curr Opin Chem Biol.2007;11(1):46-51.
[26]Caron M,Choquet-Kastylevsky G,Joubert-Caron R.Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics. 2007;6(7): 1115-1122.
[27] Sahin U, Tureci O, Schmitt H, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995;92(25): 11810-11813.
[28] Kuboshima M, Shimada H, Liu TL, et al. Identification of a novel SEREX antigen, SLC2A1/GLUT1, in esophageal squamous cell carcinoma. Int J Oncol. 2006;28(2):463-468.
[29] Ishikura H, Ikeda H, Abe H, et al. Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system. Int J Oncol. 2007;30(2):461-467.
[30] Mizukami M, Hanagiri T, Yasuda M, et al. Antitumor effect of antibody against a SEREX-defined antigen (UOEH-LC-1) on lung cancer xenotransplanted into severe combined immunodeficiency mice. Cancer Res. 2007;67(17):8351-8357.
[31] Hasegawa K, Koizumi F, Noguchi Y, et al. SSX expression in gynecological cancers and antibody response in patients. Cancer Immun. 2004;4:16.
[32] Kim Y, Jeoung D. Role of CAGE, a Novel Cancer/Testis Antigen, in Various Cellular Processes, Including Tumorigenesis, Cytolytic T Lymphocyte Induction, and Cell Motility. J Microbiol Biotechnol. 2008;18(3):600-610.
[33] Unwin RD, Harnden P, Pappin D, et al. Serological and proteomic evaluation of antibody responses in the identification of tumor antigens in renal cell carcinoma. Proteomics. 2003;3(1):45-55.
[34] Lee SY, Jeoung D. The reverse proteomics for identification of tumor antigens.J Microbiol Biotechnol. 2007;17(6):879-890.
[35] MacKeigan JP, Clements CM, Lich JD, et al. Proteomic profiling drug-induced apoptosis in non-small cell lung carcinoma: identification of RS/DJ-1 and RhoGDIalpha. Cancer Res. 2003;63(20):6928-6934.
[36] Pereira-Faca SR, Kuick R, Puravs E, et al. Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer. Cancer Res. 2007;67(24): 12000-12006.
[37] Li L, Chen SH, Yu CH, et al. Identification of hepatocellular-carcinoma-associated antigens and autoantibodies by serological proteome analysis combined with protein microarray. J Proteome Res. 2008;7(2):611-620.
[38] Jackson D, Craven RA, Hutson RC, et al. Proteomic profiling identifies afamin as a potential biomarker for ovarian cancer. Clin Cancer Res. 2007;13(24):7370-7379.
[39] Yang F, Xiao ZQ, Zhang XZ, et al. Identification of tumor antigens in human lung squamous carcinoma by serological proteome analysis. J Proteome Res. 2007;6(2):751-758.
[40] Gunawardana CG, Diamandis EP. High throughput proteomic strategies for identifying tumour-associated antigens. Cancer Lett. 2007;249(1): 110-119.
[41] Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl J Med. 2005;353(12): 1224-1235.
[42] Chen G, Wang X, Yu J, et al. Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. Cancer Res. 2007;67(7):3461-3467.
[43] Fernandez-Madrid F, Tang N, Alansari H, et al. Autoantibodies to Annexin XI-A and Other Autoantigens in the Diagnosis of Breast Cancer. Cancer Res. 2004;64(15):5089-5096.
[44] Shadidi M, Sorensen D, Dybwad A, et al. Mucosal vaccination with phage-displayed tumour antigens identified through proteomics-based strategy inhibits the growth and metastasis of 4T1 breast adenocarcinoma. Int J Oncol. 2008;32(1):241-247.
[45] Chen J, Xu XM, Underhill CB, et al. Tachyplesin activates the classic complement pathway to kill tumor cells. Cancer Res. 2005;65(11):4614-4622.
[46] Nowak JE, Chatterjee M, Mohapatra S, et al. Direct production and purification of T7 phage display cloned proteins selected and analyzed on microarrays. Biotechniques. 2006;40(2):220-227.
[47] Qiu J, Madoz-Gurpide J, Misek DE, et al. Development of natural protein microarrays for diagnosing cancer based on an antibody response to tumor antigens. J Proteome Res. 2004;3(2):261-267.
[48] Hudson ME, Pozdnyakova I, Haines K, et al. Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci U S A. 2007;104(44): 17494-17499.
[49] Madoz-Gurpide J, Kuick R, Wang H, et al. Integral protein microarrays for the identification of lung cancer antigens in sera that induce a humoral immune response.Mol Cell Proteomics.2008;7(2):268-281.
[50]Admon A,Shoshan SH.Antibodies as oncogenes:a hypothesis.Med Hypotheses.2006;67(3):471-473.
[51]Mahler V,Antoni C,Anhalt GJ,et al.Graft-versus-host-like mucocutaneous eruptions with serological features of paraneoplastic pemphigus and systemic lupus erythematosus in a patient with non-Hodgkin's lymphoma.Dermatology.1998;197(1):78-83.
[52]Kelly-Scumpia KM,Nacionales DC,Scumpia PO,et al.In vivo adjuvant activity of the RNA component of the Sm/RNP lupus autoantigen.Arthritis Rheum.2007;56(10):3379-3386.
[53]Liebes L,Potmesil M,Kim T,et al.Pharmacodynamics of topoisomerase I inhibition:Western blot determination of topoisomerase I and cleavable complex in patients with upper gastrointestinal malignancies treated with topotecan.Clin Cancer Res.1998;4(3):545-557.
[54]Al-Shukaili A,Al-Jabri AA,Al-Moundhri MS.Prognostic value of auto-antibodies in the serum of Omani patients with gastric,cancer.Saudi Med J.2006;27(12):1873-1877.
[55]Dang CV.Higher eukaryotic aminoacyl-tRNA synthetases in physiologic and pathologic states.Mol Cell Biochem.1986;71(2):107-120.
[56]Vazquez-Abad D,Carson JH,Rothfield N.Localization of histidyl-tRNA synthetase(Jo-1)in human laryngeal epithelial carcinoma cell line(HEp-2cells).Cell Tissue Res.1996;286(3):487-491.
[57]Legault D,McDermott J,Crous-Tsanaclis AM,et al.Cancer-associated myositis in the presence of anti-Jo1 autoantibodies and the antisynthetase syndrome.J Rheumatol.2008;35(1):169-171.
[58]聂轶飞,王凯娟,代丽萍,et al.肝癌相关抗原血清学自身抗体反应分析.中国公共卫生.2007;23(07):801-802.
[59]Dollinger MM,Behrens CM,Lesske J,et al.Thymostimulin in advanced hepatocellular carcinoma:a phase Ⅱ trial.BMC Cancer.2008;8(1):72.
[60]Zinkin NT,Grall F,Bhaskar K,et al.Serum proteomics,and biomarkers in hepatocellular carcinoma and chronic liver disease.Clin Cancer Res.2008;14(2):470-477.
[61]Suppiah A,Alabi A,Madden L,et al.Anti-p53 autoantibody in colorectal cancer:prognostic significance in long-term follow-up.Int J Colorectal Dis. 2008.
[62]Anderson KS,Ramachandran N,Wong J,et al.Application of Protein Microarrays for Multiplexed Detection of Antibodies to Tumor Antigens in Breast Cancer.J Proteome Res.2008;7(4):1490-1499.
[63]Chapman CJ,Murray A,McElveen JE,et al.Autoantibodies in lung cancer:possibilities for early detection and subsequent cure.Thorax.2008;63(3):228-233.
[64]刘保池,王立东,杜芳,et al.肿瘤相关抗原与自身抗体检测对食管癌早期发现和高危人群预警的意义.中华肿瘤防治杂志.2007;14(09):645-649.
[65]Nesterova M,Johnson N,Cheadle C,et al.Autoantibody biomarker opens a new gateway for cancer diagnosis.Biochim Biophys Acta.2006;1762(4):398-403.
[66]Smith RA,Cokkinides V,Eyre HJ.American Cancer Society guidelines for the early detection of cancer,2006.CA Cancer J Clin.2006;56(1):11-25;quiz 49-50.
[67]Smith RA,Cokkinides V,Eyre HJ.American Cancer Society Guidelines for the Early Detection of Cancer,2005.CA Cancer J Clin.2005;55(1):31-44;quiz 55-36.
[68]祝广峰.前列腺癌的自身抗体:针对差异表达的转录体FLJ23438和VAMP3编码抗原决定子的体液免疫应答.现代泌尿外科杂志.2007;12(01).
[69]Tomaino B,Cappello P,Capello M,et al.Autoantibody signature in human ductal pancreatic adenocarcinoma.J Proteome Res.2007;6(10):4025-4031.
[70]Agaylan A,Binder D,Sauer M,et al.A highly sensitive particle agglutination assay for the detection of P53 autoantibodies in patients with lung cancer.Cancer.2007;110(11):2502-2506.
[71]King,A.Autoantibodies as novel biomarkers for the early detection of prostate cancer.Nat Clin Pract Oncol.2006;3(1):7-8.
[72]Zhong L,Coe SP,Stromberg AJ,et al.Profiling tumor-associated antibodies for early detection of non-small cell lung cancer.J Thorac Oncol.2006;1(6):513-519.
[73]Cressey R,Pimpa S,Chewaskulyong B,et al.Simplified approaches for the development of an ELISA to detect circulating autoantibodies to p53 in cancer patients.BMC Biotechnol.2008;8:16.
[74]Fernandez Madrid F.Autoantibodies in breast cancer sera:candidate biomarkers and reporters of tumorigenesis.Cancer Lett.2005;230(2):187-198.
[75]Storr SJ,Chakrabarti J,Barnes A,et al.Use of autoantibodies in breast cancer screening and diagnosis.Expert Rev Anticancer Ther.2006;6(8):1215-1223.
[76]Lu H,Goodell V,Disis ML.Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer.J Proteome Res.2008;7(4):1388-1394.
[77]Lin HS,Talwar HS,Tarca AL,et al.Autoantibody approach for serum-based detection of head and neck cancer.Cancer Epidemiol Biomarkers Prev.2007;16(11):2396-2405.
[78]Khan S,Alvi A,Holding S,et al.The clinical significance of antinucleolar antibodies.J Clin Pathol.2008;61(3):283-286.
[79]Meffre E,Casellas R,Nussenzweig MC.Antibody regulation of B cell development.Nat Immunol.2000;1(5):379-385.
[80]Preuss KD,Zwick C,Bormann C,et al.Analysis of the B-cell repertoire against antigens expressed by human neoplasms.Immunol Rev.2002;188:43-50.
[81]Lemieux R,Bazin R.Autoantibody-induced formation of immune complexes in normal human serum.Curr Pharm Des.2006;12(2):173-179.
[82]Ehrlich JR,Tang L,Caiazzo RJ,Jr.,et al.The "Reverse Capture"Autoantibody Microarray:An Innovative Approach to Profiling the Autoantibody Response to Tissue-Derived Native Antigens.Methods Mol Biol.2008;441:175-192.