尿PCA3评分在PSA灰区诊断早期前列腺癌意义的研究
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摘要
前列腺癌是当今社会影响男性健康的最常见的恶性肿瘤之一，对男性健康的威胁逐年增加，其发病率与死亡率分别高居世界男性恶性肿瘤的第2位和第6位。在美国，前列腺癌的发病率已经超过肺癌，成为威胁男性健康的主要的恶性肿瘤。与欧美发达国家相比，亚洲人群前列腺癌的发病率较低。我国曾被认为是前列腺癌的低发国家，但是随着国内人口老龄化步伐的加快、饮食习惯的西方化以及前列腺癌诊治水平的不断提高，我国前列腺癌的发病率正逐年上升。据资料统计，2009年前列腺癌的发病率及死亡率与2003年比较，分别升高了51.91%和64.96%。现阶段，在临床上广泛应用于前列腺癌筛查的实验室检查是测定血清PSA的水平。但PSA无前列腺癌特异性，由于前列腺炎、急性尿潴留、膀胱镜检查、导尿和直肠指诊等，均可能会造成血清PSA水平增高，导致诊断的特异性降低。因此，临床上迫切需要寻找一种新的前列腺癌特异性肿瘤标志物，以便提高早期前列腺癌的诊断率。
PCA3为前列腺癌特异性基因，在前列腺癌组织中高表达，在正常前列腺组织中不表达或低表达，在非前列腺癌的癌组织中不表达。随着近几年对于PCA3的研究，发现尿PCA3评分对于前列腺癌的诊断具有极高的价值可以为血清PSA升高的患者是否需行前列腺穿刺活检，以及对于初次活检阴性的患者是否需行二次前列腺穿刺活检提供依据。但是，在血清PSA灰区范围内，尿PCA3评分在诊断早期前列腺癌的应用价值尚无大宗病例报道。基于以上原因，本实验通过细胞培养、RNA提取、逆转录、酶联免疫、RNA凝胶电泳、HE染色、免疫组化及RT-qPCR等实验技术，从而明确尿PCA3评分在血清PSA灰区内诊断早期前列腺癌的意义。
研究结果：
1、在细胞学层面研究，应用RT-qPCR技术得出前列腺癌细胞株LNCaP的PCA3的基因表达量为72.21±42.43；正常前列腺上皮细胞株RWPE-1的PCA3的基因表达量为9.35±6.72；膀胱癌细胞株T24中，无PCA3基因的表达。PCA3基因表达量在前列腺癌细胞株LNCaP与正常前列腺上皮细胞株RWPE-1比较，有显著性差异（P=0.0002），说明PCA3mRNA高表达于前列腺癌细胞中。
2、应用RT-qPCR技术，得出尿PCA3评分在不同分组中的表达量：前列腺癌组为164.84±133.24，良性前列腺增生组为31.41±12.42，健康对照组为15.37±8.10。前列腺癌组的尿PCA3评分分别与良性前列腺增生组和健康对照组的尿PCA3评分比较，P值均小于0.000，差异具有统计学意义，说明前列腺癌组的尿PCA3评分明显高于良性前列腺增生组及健康对照组；并且，尿PCA3评分经ROC曲线分析，将截断值定为47.8时，敏感度和特异度分别为74.3%和89.0%，阳性预测者值和阴性预测值分别为73.3%和90.1%。
3、通过血PSA检测及排除标准，共有243名血清PSA在4~10ng/ml的患者入组。其中经病理学诊断为前列腺癌的患者为22名，良性前列腺增生的患者为221名。以47.8为尿PCA3评分截断值时，尿PCA3评分阳性表达的为23人，阴性表达的为220人。在22名前列腺癌患者中，尿PCA3评分阳性表达的17例，阴性表达的5例，在221例前列腺增生的患者中，尿PCA3评分阳性表达的6例，阴性表达的215例。尿PCA3评分在血清PSA灰区范围内诊断前列腺癌的敏感性和特异性分别为77.3%和97.3%，阳性预测值和阴性预测值分别为73.9%和97.7%。对于尿PCA3评分为阳性表达的6例前列腺增生患者，在1个月后再次行前列腺穿刺活检，另有2例诊断为前列腺癌。其余4例患者随访1年，分别于二次穿刺活检后3个月、6个月、9个月及12个月各检测1次血清PSA，因血清PSA未见明显升高，建议继续随诊观察。
研究结论：
1、PCA3基因特异性的高表达于前列腺癌细胞，在正常前列腺上皮细胞呈低表达，在非前列腺癌细胞的其他癌细胞中不表达。
2、尿PCA3评分对于前列腺癌的诊断，具有很高的敏感性和特异性。
3、本实验中，以47.8作为尿PCA3评分的截断值，对于诊断前列腺癌具有较高的敏感度、特异度、阳性预测值和阴性预测值。
4、尿PCA3评分在血清PSA灰区范围内可以提高早期前列腺癌的诊断率；
5、尿PCA3评分对于二次前列腺穿刺活检具有明确的指导意义。
总之，在血清PSA位于灰区范围内的患者，同时结合尿PCA3评分的检测，选择合适的尿PCA3评分截断值进行判断，不仅可以避免不必要的经直肠超声引导下的前列腺穿刺活检，降低患者的痛苦，而且可以协助提高早期前列腺癌的诊断率，减少漏诊，防止疾病的进展影响患者的预后。因此，尿PCA3评分在血清PSA灰区范围内诊断早期前列腺癌具有显著性的意义。
Prostate cancer (PCa) is considered one of the most common malemalignant tumor nowadays. The threatens from PCa have been increasing yearby year. The morbidity and mortality ranks No.2and No.6around the world. InU.S., the morbidity of PCa has already exceeded lung cancer and proved to bethe top malignant tumor threatening male health. Asian populations, includingChinese, used to be regarded with lower morbidities of PCa, comparing with thepopulations in Europe and U.S.. The morbidity and mortality of PCa in year2009were51.91%and64.96%higher than those in year2003. Prostate specificantigen (PSA) test is widely used in clinical screening PCa. However, PSA canhardly be deemed as PCa specific. Many factors such as prostate inflammation,acute retention of urine, cystoscope examination, catheterization and rectaltouch can lead to the increase in serum PSA levels. The misunderstanding of theresults of PSA levels can severely disrupt the clinical diagnosis. Therefore, anovel PCa specific marker is required for more effective early diagnosis.
Prostate cancer antigen3(PCA3), a PCa specific gene, has been found withhigh expression in PCa tissues, extremely low expression in healthy prostatetissues and usually no expression in non prostate tissues. PCA3score offers avaluable evidence on whether a prostate biopsy is necessary for the patient with increased serum PSA level or the patient with negative prostate biopsy results.Until now, no studies has ever shown PCA3score has been largely adopted toevaluate serum PSA gray zone. In our research, we try to elucidate the roles ofPCA3score in diagnose of early PCa within serum PSA gray zone by series oftechnologies such as cell culture, RNA preparation, reverse transcription, ELISA,RNA electrophoresis, HE staining, immunohistology and RT-qPCR.
Results:
1. The expression level of PCA3in LNCap cell line was significantly lowerthan that in RWPE-1(72.21±42.43vs.9.35±6.72, P=0.0002). No PCA3wasexpressed in T24cell line. The result indicates PCA3mRNA is highly expressedin PCa cells.
2. The urinary PCA3score of PCa group was significantly higher than thatof benign prostate hyperplasia group and control group (164.84±133.24vs.31.41±12.42, p <0.05;164.84±133.24vs.15.37±8.10, p <0.000; respectively).The results indicate that PCa group has a obviously higher PCA3score thanbenign prostate hyperplasia group and control group. Furthermore, in the ROCanalyze of PCA3score, when the ROC cut-off is47.8, the sensitivity andspecificity are74.3%and89.0%, meanwhile the positive and negative predictivevalue are73.3%and90.1%.
3. We have identified243patients within serum PSA gray zone after serumPSA test and samples exclusion.22out of243have been pathologicallydiagnosed as PCa and the rest221were benign prostate hyperplasia (BPH) patients. Out of all243patients,23cases had urinary PCA3score positiveexpressions when ROC cut-off value was set as47.8, and221cases had urinaryPCA3score negative expressions. Out of22PCa patients,17cases had urinaryPCA score positive expressions, while5cases had urinary PCA score negativeexpressions. Out of221BPH patients,6cases had urinary PCA score positiveexpressions, and the rest215cases were negative expressions. The sensitivityand specificity of urinary PCA3score in diagnosing early PCa within gray zoneare77.3%and97.3%. The positive and negative predictive values are73.9%and97.7%. After1month, biopsy results of6BPH patients with uriniary PCA3score positive expression showed2cases had been diagnosed as PCa. The serumPSA levels of the rest4patients after3,6,9and12months showed no credibleincrease, therefore it was suggested to keep on follow-up visits.
Conclusions:
1. PCA3is highly and specifically expressed in PCa cells. The expressionlevel in healthy prostate cells is low. No PCA3is found being expressed in nonPCa cells.
2. Urinary PCA3score is highly sensitive and specific for diagnosing earlyprostate cancer.
3. In our study,47.8has been proved to be a proper urinary PCA3scorecut-off value with high sensitivity, specificity, positive and negative predictionfor diagnosis of early PCa.
4. Urinary PCA3score is able to raise the effects of diagnosis of early PCa within serum PSA gray zone.
5. The second biopsy test can be suggested by urinary PCA3score.
In conclusion, PCA3score with proper cut-off value is beneficial inavoiding unnecessary painful biopsy and raising effects of diagnosis of earlyPCa. A good prognosis is believed to be predicted under the suggestion of PCA3score. Thus, PCA3score has positive effects in the diagnosis of early PCa withinserum PSA gray zone.
PCA3为前列腺癌特异性基因，在前列腺癌组织中高表达，在正常前列腺组织中不表达或低表达，在非前列腺癌的癌组织中不表达。随着近几年对于PCA3的研究，发现尿PCA3评分对于前列腺癌的诊断具有极高的价值可以为血清PSA升高的患者是否需行前列腺穿刺活检，以及对于初次活检阴性的患者是否需行二次前列腺穿刺活检提供依据。但是，在血清PSA灰区范围内，尿PCA3评分在诊断早期前列腺癌的应用价值尚无大宗病例报道。基于以上原因，本实验通过细胞培养、RNA提取、逆转录、酶联免疫、RNA凝胶电泳、HE染色、免疫组化及RT-qPCR等实验技术，从而明确尿PCA3评分在血清PSA灰区内诊断早期前列腺癌的意义。
研究结果：
1、在细胞学层面研究，应用RT-qPCR技术得出前列腺癌细胞株LNCaP的PCA3的基因表达量为72.21±42.43；正常前列腺上皮细胞株RWPE-1的PCA3的基因表达量为9.35±6.72；膀胱癌细胞株T24中，无PCA3基因的表达。PCA3基因表达量在前列腺癌细胞株LNCaP与正常前列腺上皮细胞株RWPE-1比较，有显著性差异（P=0.0002），说明PCA3mRNA高表达于前列腺癌细胞中。
2、应用RT-qPCR技术，得出尿PCA3评分在不同分组中的表达量：前列腺癌组为164.84±133.24，良性前列腺增生组为31.41±12.42，健康对照组为15.37±8.10。前列腺癌组的尿PCA3评分分别与良性前列腺增生组和健康对照组的尿PCA3评分比较，P值均小于0.000，差异具有统计学意义，说明前列腺癌组的尿PCA3评分明显高于良性前列腺增生组及健康对照组；并且，尿PCA3评分经ROC曲线分析，将截断值定为47.8时，敏感度和特异度分别为74.3%和89.0%，阳性预测者值和阴性预测值分别为73.3%和90.1%。
3、通过血PSA检测及排除标准，共有243名血清PSA在4~10ng/ml的患者入组。其中经病理学诊断为前列腺癌的患者为22名，良性前列腺增生的患者为221名。以47.8为尿PCA3评分截断值时，尿PCA3评分阳性表达的为23人，阴性表达的为220人。在22名前列腺癌患者中，尿PCA3评分阳性表达的17例，阴性表达的5例，在221例前列腺增生的患者中，尿PCA3评分阳性表达的6例，阴性表达的215例。尿PCA3评分在血清PSA灰区范围内诊断前列腺癌的敏感性和特异性分别为77.3%和97.3%，阳性预测值和阴性预测值分别为73.9%和97.7%。对于尿PCA3评分为阳性表达的6例前列腺增生患者，在1个月后再次行前列腺穿刺活检，另有2例诊断为前列腺癌。其余4例患者随访1年，分别于二次穿刺活检后3个月、6个月、9个月及12个月各检测1次血清PSA，因血清PSA未见明显升高，建议继续随诊观察。
研究结论：
1、PCA3基因特异性的高表达于前列腺癌细胞，在正常前列腺上皮细胞呈低表达，在非前列腺癌细胞的其他癌细胞中不表达。
2、尿PCA3评分对于前列腺癌的诊断，具有很高的敏感性和特异性。
3、本实验中，以47.8作为尿PCA3评分的截断值，对于诊断前列腺癌具有较高的敏感度、特异度、阳性预测值和阴性预测值。
4、尿PCA3评分在血清PSA灰区范围内可以提高早期前列腺癌的诊断率；
5、尿PCA3评分对于二次前列腺穿刺活检具有明确的指导意义。
总之，在血清PSA位于灰区范围内的患者，同时结合尿PCA3评分的检测，选择合适的尿PCA3评分截断值进行判断，不仅可以避免不必要的经直肠超声引导下的前列腺穿刺活检，降低患者的痛苦，而且可以协助提高早期前列腺癌的诊断率，减少漏诊，防止疾病的进展影响患者的预后。因此，尿PCA3评分在血清PSA灰区范围内诊断早期前列腺癌具有显著性的意义。
Prostate cancer (PCa) is considered one of the most common malemalignant tumor nowadays. The threatens from PCa have been increasing yearby year. The morbidity and mortality ranks No.2and No.6around the world. InU.S., the morbidity of PCa has already exceeded lung cancer and proved to bethe top malignant tumor threatening male health. Asian populations, includingChinese, used to be regarded with lower morbidities of PCa, comparing with thepopulations in Europe and U.S.. The morbidity and mortality of PCa in year2009were51.91%and64.96%higher than those in year2003. Prostate specificantigen (PSA) test is widely used in clinical screening PCa. However, PSA canhardly be deemed as PCa specific. Many factors such as prostate inflammation,acute retention of urine, cystoscope examination, catheterization and rectaltouch can lead to the increase in serum PSA levels. The misunderstanding of theresults of PSA levels can severely disrupt the clinical diagnosis. Therefore, anovel PCa specific marker is required for more effective early diagnosis.
Prostate cancer antigen3(PCA3), a PCa specific gene, has been found withhigh expression in PCa tissues, extremely low expression in healthy prostatetissues and usually no expression in non prostate tissues. PCA3score offers avaluable evidence on whether a prostate biopsy is necessary for the patient with increased serum PSA level or the patient with negative prostate biopsy results.Until now, no studies has ever shown PCA3score has been largely adopted toevaluate serum PSA gray zone. In our research, we try to elucidate the roles ofPCA3score in diagnose of early PCa within serum PSA gray zone by series oftechnologies such as cell culture, RNA preparation, reverse transcription, ELISA,RNA electrophoresis, HE staining, immunohistology and RT-qPCR.
Results:
1. The expression level of PCA3in LNCap cell line was significantly lowerthan that in RWPE-1(72.21±42.43vs.9.35±6.72, P=0.0002). No PCA3wasexpressed in T24cell line. The result indicates PCA3mRNA is highly expressedin PCa cells.
2. The urinary PCA3score of PCa group was significantly higher than thatof benign prostate hyperplasia group and control group (164.84±133.24vs.31.41±12.42, p <0.05;164.84±133.24vs.15.37±8.10, p <0.000; respectively).The results indicate that PCa group has a obviously higher PCA3score thanbenign prostate hyperplasia group and control group. Furthermore, in the ROCanalyze of PCA3score, when the ROC cut-off is47.8, the sensitivity andspecificity are74.3%and89.0%, meanwhile the positive and negative predictivevalue are73.3%and90.1%.
3. We have identified243patients within serum PSA gray zone after serumPSA test and samples exclusion.22out of243have been pathologicallydiagnosed as PCa and the rest221were benign prostate hyperplasia (BPH) patients. Out of all243patients,23cases had urinary PCA3score positiveexpressions when ROC cut-off value was set as47.8, and221cases had urinaryPCA3score negative expressions. Out of22PCa patients,17cases had urinaryPCA score positive expressions, while5cases had urinary PCA score negativeexpressions. Out of221BPH patients,6cases had urinary PCA score positiveexpressions, and the rest215cases were negative expressions. The sensitivityand specificity of urinary PCA3score in diagnosing early PCa within gray zoneare77.3%and97.3%. The positive and negative predictive values are73.9%and97.7%. After1month, biopsy results of6BPH patients with uriniary PCA3score positive expression showed2cases had been diagnosed as PCa. The serumPSA levels of the rest4patients after3,6,9and12months showed no credibleincrease, therefore it was suggested to keep on follow-up visits.
Conclusions:
1. PCA3is highly and specifically expressed in PCa cells. The expressionlevel in healthy prostate cells is low. No PCA3is found being expressed in nonPCa cells.
2. Urinary PCA3score is highly sensitive and specific for diagnosing earlyprostate cancer.
3. In our study,47.8has been proved to be a proper urinary PCA3scorecut-off value with high sensitivity, specificity, positive and negative predictionfor diagnosis of early PCa.
4. Urinary PCA3score is able to raise the effects of diagnosis of early PCa within serum PSA gray zone.
5. The second biopsy test can be suggested by urinary PCA3score.
In conclusion, PCA3score with proper cut-off value is beneficial inavoiding unnecessary painful biopsy and raising effects of diagnosis of earlyPCa. A good prognosis is believed to be predicted under the suggestion of PCA3score. Thus, PCA3score has positive effects in the diagnosis of early PCa withinserum PSA gray zone.
引文
[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin,2011,61(2):69-90.
[2] Jemal A, Siegel R, Xu J, et al. Cancer statistics,2010. CA Cancer J Clin,2010,60(5):277-300.
[3] Batura D andGopal Rao G. The national burden of infections after prostate biopsy inEngland and Wales: a wake-up call for better prevention. J Antimicrob Chemother,2013,68(2):247-249.
[4] Sim HG andCheng CW. Changing demography of prostate cancer in Asia. Eur J Cancer,2005,41(6):834-845.
[5] Salem S, Salahi M, Mohseni M, et al. Major dietary factors and prostate cancer risk: aprospective multicenter case-control study. Nutr Cancer,2011,63(1):21-27.
[6] Leitzmann MF and Rohrmann S. Risk factors for the onset of prostatic cancer: age,location, and behavioral correlates. Clin Epidemiol,2012,4:1-11.
[7] Song Y, Chavarro JE, Cao Y, et al. Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians. J Nutr,2013,143(2):189-196.
[8] Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in2008:GLOBOCAN2008. Int J Cancer,2010,127(12):2893-2917.
[9]毕新刚,韩仁强,周金意,等.2009年中国前列腺癌发病和死亡分析.中国肿瘤,2013,22(6):417-422.
[10] Zincke H, Oesterling JE, Blute ML, et al. Long-term (15years) results after radicalprostatectomy for clinically localized (stage T2c or lower) prostate cancer. J Urol,1994,152(5Pt2):1850-1857.
[11] Paulson DF, Moul JW and Walther PJ. Radical prostatectomy for clinical stageT1-2N0M0prostatic adenocarcinoma: long-term results. J Urol,1990,144(5):1180-1184.
[12] Aus G, Abbou CC, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol,2005,48(4):546-551.
[13] Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality ina randomized European study. N Engl J Med,2009,360(13):1320-1328.
[14] Andriole GL, Crawford ED, Grubb RL, et al. Mortality results from a randomizedprostate-cancer screening trial. N Engl J Med,2009,360(13):1310-1319.
[15] Morote J, Fernandez S, Alana L, et al. PTOV1expression predicts prostate cancer inmen with isolated high-grade prostatic intraepithelial neoplasia in needle biopsy. ClinCancer Res,2008,14(9):2617-2622.
[16] Zarghami N and Diamandis EP. Detection of prostate-specific antigen mRNA andprotein in breast tumors. Clin Chem,1996,42(3):361-366.
[17] Zarghami N, Levesque M, D'Costa M, et al. Frequency of expression of prostate-specific antigen mRNA in lung tumors. Am J Clin Pathol,1997,108(2):184-190.
[18] Pannek J and Partin AW. Prostate-specific antigen: what's new in1997. Oncology(Williston Park),1997,11(9):1273-1278; discussion1279-1282.
[19] Loeb S and Catalona WJ. What to do with an abnormal PSA test. Oncologist,2008,13(3):299-305.
[20] Reed AB and Parekh DJ. Biomarkers for prostate cancer detection. Expert RevAnticancer Ther,2010,10(1):103-114.
[21]李鸣,那彦群.不同水平前列腺特异抗原的前列腺癌诊断率.中华医学杂志,2008,88(1):16-18.
[22] Gao HW, Li YL, Wu S, et al. Mass screening of prostate cancer in a Chinese population:the relationship between pathological features of prostate cancer and serum prostatespecific antigen. Asian J Androl,2005,7(2):159-163.
[23] Morote J, Trilla E, Esquena S, et al. The percentage of free prostatic-specific antigen isalso useful in men with normal digital rectal examination and serum prostatic-specificantigen between10.1and20ng/ml. Eur Urol,2002,42(4):333-337.
[24] Aus G, Damber JE, Khatami A, et al. Individualized screening interval for prostatecancer based on prostate-specific antigen level: results of a prospective, randomized,population-based study. Arch Intern Med,2005,165(16):1857-1861.
[25] Nam RK, Zhang WW, Trachtenberg J, et al. Utility of incorporating genetic variants forthe early detection of prostate cancer. Clin Cancer Res,2009,15(5):1787-1793.
[26] Mistry K and Cable G. Meta-analysis of prostate-specific antigen and digital rectalexamination as screening tests for prostate carcinoma. J Am Board Fam Pract,2003,16(2):95-101.
[27] Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from theProstate Cancer Prevention Trial. J Natl Cancer Inst,2006,98(8):529-534.
[28] Lin DW. Beyond PSA: utility of novel tumor markers in the setting of elevated PSA.Urol Oncol,2009,27(3):315-321.
[29] Steineck G, Helgesen F, Adolfsson J, et al. Quality of life after radical prostatectomy orwatchful waiting. N Engl J Med,2002,347(11):790-796.
[30] Litwin MS, Gore JL, Kwan L, et al. Quality of life after surgery, external beamirradiation, or brachytherapy for early-stage prostate cancer. Cancer,2007,109(11):2239-2247.
[31] Barry MJ. Screening for prostate cancer--the controversy that refuses to die. N Engl JMed,2009,360(13):1351-1354.
[32] Goessl C, Krause H, Muller M, et al. Fluorescent methylation-specific polymerase chainreaction for DNA-based detection of prostate cancer in bodily fluids. Cancer Res,2000,60(21):5941-5945.
[33] Hoque MO, Topaloglu O, Begum S, et al. Quantitative methylation-specific polymerasechain reaction gene patterns in urine sediment distinguish prostate cancer patients fromcontrol subjects. J Clin Oncol,2005,23(27):6569-6575.
[34] Roupret M, Hupertan V, Yates DR, et al. Molecular detection of localized prostatecancer using quantitative methylation-specific PCR on urinary cells obtained followingprostate massage. Clin Cancer Res,2007,13(6):1720-1725.
[35] Laxman B, Tomlins SA, Mehra R, et al. Noninvasive detection of TMPRSS2:ERGfusion transcripts in the urine of men with prostate cancer. Neoplasia,2006,8(10):885-888.
[36] Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethalprostate cancer in a watchful waiting cohort. Oncogene,2007,26(31):4596-4599.
[37] Thuret R, Chantrel-Groussard K, Azzouzi AR, et al. Clinical relevance of geneticinstability in prostatic cells obtained by prostatic massage in early prostate cancer. Br JCancer,2005,92(2):236-240.
[38] Sun J, Zheng SL, Wiklund F, et al. Sequence variants at22q13are associated withprostate cancer risk. Cancer Res,2009,69(1):10-15.
[39] Hsu FC, Sun J, Wiklund F, et al. A novel prostate cancer susceptibility locus at19q13.Cancer Res,2009,69(7):2720-2723.
[40] Mikolajczyk SD, Grauer LS, Millar LS, et al. A precursor form of PSA (pPSA) is acomponent of the free PSA in prostate cancer serum. Urology,1997,50(5):710-714.
[41] Mikolajczyk SD, Millar LS, Wang TJ, et al."BPSA," a specific molecular form of freeprostate-specific antigen, is found predominantly in the transition zone of patients withnodular benign prostatic hyperplasia. Urology,2000,55(1):41-45.
[42] Mikolajczyk SD, Marks LS, Partin AW, et al. Free prostate-specific antigen in serum isbecoming more complex. Urology,2002,59(6):797-802.
[43] Recker F, Kwiatkowski MK, Piironen T, et al. Human glandular kallikrein as a tool toimprove discrimination of poorly differentiated and non-organ-confined prostate cancercompared with prostate-specific antigen. Urology,2000,55(4):481-485.
[44] Luo J, Zha S, Gage WR, et al. Alpha-methylacyl-CoA racemase: a new molecularmarker for prostate cancer. Cancer Res,2002,62(8):2220-2226.
[45]王科峰,吴斌.脂肪酸合成酶与前列腺癌.中华男科学杂志,2008,14(8):740-742.
[46] Mhawech-Fauceglia P, Zhang S, Terracciano L, et al. Prostate-specific membraneantigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivityand specificity in prostate adenocarcinoma: an immunohistochemical study usingmutiple tumour tissue microarray technique. Histopathology,2007,50(4):472-483.
[47]郎根强,孙颖浩,许传亮,等.前列腺癌组织中前列腺干细胞抗原的表达及其意义.临床泌尿外科杂志,2003,18(1):27-29.
[48] Paul B, Dhir R, Landsittel D, et al. Detection of prostate cancer with a blood-basedassay for early prostate cancer antigen. Cancer Res,2005,65(10):4097-4100.
[49] Voloshyna I, Besana A, Castillo M, et al. TREK-1is a novel molecular target in prostatecancer. Cancer Res,2008,68(4):1197-1203.
[50] Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl JMed,2005,353(12):1224-1235.
[51] Bussemakers MJ, van Bokhoven A, Verhaegh GW, et al. DD3: a new prostate-specificgene, highly overexpressed in prostate cancer. Cancer Res,1999,59(23):5975-5879.
[52]陈占国,陈伟,陶志华,等.基因测序筛选前列腺癌患者PCA3(DD3)基因外显子多态性.中国男科学杂志,2009,23(11):10-13.
[53] de Kok JB, Verhaegh GW, Roelofs RW, et al. DD3(PCA3), a very sensitive and specificmarker to detect prostate tumors. Cancer Res,2002,62(9):2695-2698.
[54] Jung M, Xu C, Spethmann J, et al. Re: Hessels D, Klein Gunnewiek JMT, van Oort I,Karthaus HFM, van Leenders GJL, van Balken B, Kiemeney LA, Witjes JA, SchalkenJA. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. EurUrol2003;44:8-16. Eur Urol,2004,46(2):271-272.
[55] Hessels D, Klein Gunnewiek JM, van Oort I, et al. DD3(PCA3)-based molecular urineanalysis for the diagnosis of prostate cancer. Eur Urol,2003,44(1):8-15; discussion15-16.
[56] Fradet Y, Saad F, Aprikian A, et al. uPM3, a new molecular urine test for the detectionof prostate cancer. Urology,2004,64(2):311-315; discussion315-316.
[57] Groskopf J, Aubin SM, Deras IL, et al. APTIMA PCA3molecular urine test:development of a method to aid in the diagnosis of prostate cancer. Clin Chem,2006,52(6):1089-1095.
[58] Nyberg M, Ulmert D, Lindgren A, et al. PCA3as a diagnostic marker for prostatecancer: a validation study on a Swedish patient population. Scand J Urol Nephrol,2010,44(6):378-383.
[59] Shen M, Chen W, Yu K, et al. The diagnostic value of PCA3gene-based analysis ofurine sediments after digital rectal examination for prostate cancer in a Chinesepopulation. Exp Mol Pathol,2011,90(1):97-100.
[60] Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer amongmen with a prostate-specific antigen level [61] Deras IL, Aubin SM, Blase A, et al. PCA3: a molecular urine assay for predictingprostate biopsy outcome. J Urol,2008,179(4):1587-1592.
[62] Pepe P, Fraggetta F, Galia A, et al. PCA3score and prostate cancer diagnosis at repeatedsaturation biopsy. Which cut-off:20or35? Int Braz J Urol,2012,38(4):489-495.
[63] Augustin H, Mayrhofer K, Pummer K, et al. Relationship between prostate cancer gene3(PCA3) and characteristics of tumor aggressiveness. Prostate,2013,73(2):203-210.
[64] van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, et al. Detailed analysis ofhistopathological parameters in radical prostatectomy specimens and PCA3urine testresults. Prostate,2008,68(11):1215-1222.
[65] Haese A, de la Taille A, van Poppel H, et al. Clinical utility of the PCA3urine assay inEuropean men scheduled for repeat biopsy. Eur Urol,2008,54(5):1081-1088.
[66] Nakanishi H, Groskopf J, Fritsche HA, et al. PCA3molecular urine assay correlateswith prostate cancer tumor volume: implication in selecting candidates for activesurveillance. J Urol,2008,179(5):1804-1809; discussion1809-1810.
[67]刘光香,郭宏骞,李笑弓,等. PCA3在前列腺癌患者前列腺按摩后尿液中的表达.现代泌尿外科杂志,2009,14(1):18-21.
[68] Klatte T, Waldert M, de Martino M, et al. Age-specific PCA3score reference values fordiagnosis of prostate cancer. World J Urol,2012,30(3):405-410.
[69] Tombal B, Andriole GL, de la Taille A, et al. Clinical judgment versus biomarkerprostate cancer gene3: which is best when determining the need for repeat prostatebiopsy? Urology,2013,81(5):998-1004.
[70] Tinzl M, Marberger M, Horvath S, et al. DD3PCA3RNA analysis in urine--a newperspective for detecting prostate cancer. Eur Urol,2004,46(2):182-186; discussion187.
[71] van Gils MP, Hessels D, van Hooij O, et al. The time-resolved fluorescence-basedPCA3test on urinary sediments after digital rectal examination; a Dutch multicentervalidation of the diagnostic performance. Clin Cancer Res,2007,13(3):939-943.
[72] Marks LS, Fradet Y, Deras IL, et al. PCA3molecular urine assay for prostate cancer inmen undergoing repeat biopsy. Urology,2007,69(3):532-535.
[73] Hessels D and Schalken JA. The use of PCA3in the diagnosis of prostate cancer. NatRev Urol,2009,6(5):255-261.
[74] van Gils MP, Cornel EB, Hessels D, et al. Molecular PCA3diagnostics on prostaticfluid. Prostate,2007,67(8):881-887.
[75] Fontenete S, Silva J, Teixeira AL, et al. Controversies in using urine samples forProstate Cancer detection: PSA and PCA3expression analysis. Int Braz J Urol,2011,37(6):719-726.
[76] Thomas CE, Sexton W, Benson K, et al. Urine collection and processing for proteinbiomarker discovery and quantification. Cancer Epidemiol Biomarkers Prev,2010,19(4):953-959.
[77] Medeiros M, Sharma VK, Ding R, et al. Optimization of RNA yield, purity and mRNAcopy number by treatment of urine cell pellets with RNAlater. J Immunol Methods,2003,279(1-2):135-142.
[78] Tichopad A, Didier A and Pfaffl MW. Inhibition of real-time RT-PCR quantification dueto tissue-specific contaminants. Mol Cell Probes,2004,18(1):45-50.
[79] Batura D and Gopal Rao G. The national burden of infections after prostate biopsy inEngland and Wales: a wake-up call for better prevention--authors' response. JAntimicrob Chemother,2013,68(10):2419-2420.
[80] Ramos CG, Valdevenito R, Vergara I, et al. PCA3sensitivity and specificity for prostatecancer detection in patients with abnormal PSA and/or suspicious digital rectalexamination. First Latin American experience. Urol Oncol,2013,31(8):1522-1526.
[81] Ochiai A, Okihara K, Kamoi K, et al. Clinical utility of the prostate cancer gene3(PCA3) urine assay in Japanese men undergoing prostate biopsy. BJU Int,2013,111(6):928-933.
[82] Capoluongo E, Zambon CF, Basso D, et al. PCA3score of20could improve prostatecancer detection: results obtained on734Italian individuals. Clin Chim Acta,2014,429:46-50.·[83] Salagierski M, Mulders P and Schalken JA. Predicting prostate biopsy outcome using aPCA3-based nomogram in a Polish cohort. Anticancer Res,2013,33(2):553-557.
[84] van Bokhoven A, Varella-Garcia M, Korch C, et al. Molecular characterization ofhuman prostate carcinoma cell lines. Prostate,2003,57(3):205-225.
[85] Landers KA, Burger MJ, Tebay MA, et al. Use of multiple biomarkers for a moleculardiagnosis of prostate cancer. Int J Cancer,2005.114(6):950-956.
[86]陶志华,毛晓露,王彩虹,等. DD3mRNA在前列腺癌组织中定量表达分析.中华男科学杂志,2007,13(2):130-133.
[87] Meng FJ, Shan A, Jin L, et al. The expression of a variant prostate-specific antigen inhuman prostate. Cancer Epidemiol Biomarkers Prev,2002,11(3):305-309.
[88] Shappell SB, Fulmer J, Arguello D, et al. PCA3urine mRNA testing for prostatecarcinoma: patterns of use by community urologists and assay performance in referencelaboratory setting. Urology,2009,73(2):363-368.
[89] Wang R, Chinnaiyan AM, Dunn RL, et al. Rational approach to implementation ofprostate cancer antigen3into clinical care. Cancer,2009,115(17):3879-3886.
[90] Ng CF, Yeung R, Chiu PK, et al. The role of urine prostate cancer antigen3mRNAlevels in the diagnosis of prostate cancer among Hong Kong Chinese patients. HongKong Med J,2012,18(6):459-465.
[91] Crawford ED, Rove KO, Trabulsi EJ, et al. Diagnostic performance of PCA3to detectprostate cancer in men with increased prostate specific antigen: a prospective study of1,962cases. J Urol,2012,188(5):1726-1731.
[92] Chevli KK, Duff M, Walter P, et al. Urinary PCA3as a Predictor of Prostate Cancer in aCohort of3,073Men Undergoing Initial Prostate Biopsy. J Urol,2013.
[93] Marks LS and Bostwick DG. Prostate Cancer Specificity of PCA3Gene Testing:Examples from Clinical Practice. Rev Urol,2008,10(3):175-181.
[94] Ruffion A, Devonec M, Champetier D, et al. PCA3and PCA3-based nomogramsimprove diagnostic accuracy in patients undergoing first prostate biopsy. Int J Mol Sci,2013,14(9):17767-17780.
[2] Jemal A, Siegel R, Xu J, et al. Cancer statistics,2010. CA Cancer J Clin,2010,60(5):277-300.
[3] Batura D andGopal Rao G. The national burden of infections after prostate biopsy inEngland and Wales: a wake-up call for better prevention. J Antimicrob Chemother,2013,68(2):247-249.
[4] Sim HG andCheng CW. Changing demography of prostate cancer in Asia. Eur J Cancer,2005,41(6):834-845.
[5] Salem S, Salahi M, Mohseni M, et al. Major dietary factors and prostate cancer risk: aprospective multicenter case-control study. Nutr Cancer,2011,63(1):21-27.
[6] Leitzmann MF and Rohrmann S. Risk factors for the onset of prostatic cancer: age,location, and behavioral correlates. Clin Epidemiol,2012,4:1-11.
[7] Song Y, Chavarro JE, Cao Y, et al. Whole milk intake is associated with prostate cancer-specific mortality among U.S. male physicians. J Nutr,2013,143(2):189-196.
[8] Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in2008:GLOBOCAN2008. Int J Cancer,2010,127(12):2893-2917.
[9]毕新刚,韩仁强,周金意,等.2009年中国前列腺癌发病和死亡分析.中国肿瘤,2013,22(6):417-422.
[10] Zincke H, Oesterling JE, Blute ML, et al. Long-term (15years) results after radicalprostatectomy for clinically localized (stage T2c or lower) prostate cancer. J Urol,1994,152(5Pt2):1850-1857.
[11] Paulson DF, Moul JW and Walther PJ. Radical prostatectomy for clinical stageT1-2N0M0prostatic adenocarcinoma: long-term results. J Urol,1990,144(5):1180-1184.
[12] Aus G, Abbou CC, Bolla M, et al. EAU guidelines on prostate cancer. Eur Urol,2005,48(4):546-551.
[13] Schroder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality ina randomized European study. N Engl J Med,2009,360(13):1320-1328.
[14] Andriole GL, Crawford ED, Grubb RL, et al. Mortality results from a randomizedprostate-cancer screening trial. N Engl J Med,2009,360(13):1310-1319.
[15] Morote J, Fernandez S, Alana L, et al. PTOV1expression predicts prostate cancer inmen with isolated high-grade prostatic intraepithelial neoplasia in needle biopsy. ClinCancer Res,2008,14(9):2617-2622.
[16] Zarghami N and Diamandis EP. Detection of prostate-specific antigen mRNA andprotein in breast tumors. Clin Chem,1996,42(3):361-366.
[17] Zarghami N, Levesque M, D'Costa M, et al. Frequency of expression of prostate-specific antigen mRNA in lung tumors. Am J Clin Pathol,1997,108(2):184-190.
[18] Pannek J and Partin AW. Prostate-specific antigen: what's new in1997. Oncology(Williston Park),1997,11(9):1273-1278; discussion1279-1282.
[19] Loeb S and Catalona WJ. What to do with an abnormal PSA test. Oncologist,2008,13(3):299-305.
[20] Reed AB and Parekh DJ. Biomarkers for prostate cancer detection. Expert RevAnticancer Ther,2010,10(1):103-114.
[21]李鸣,那彦群.不同水平前列腺特异抗原的前列腺癌诊断率.中华医学杂志,2008,88(1):16-18.
[22] Gao HW, Li YL, Wu S, et al. Mass screening of prostate cancer in a Chinese population:the relationship between pathological features of prostate cancer and serum prostatespecific antigen. Asian J Androl,2005,7(2):159-163.
[23] Morote J, Trilla E, Esquena S, et al. The percentage of free prostatic-specific antigen isalso useful in men with normal digital rectal examination and serum prostatic-specificantigen between10.1and20ng/ml. Eur Urol,2002,42(4):333-337.
[24] Aus G, Damber JE, Khatami A, et al. Individualized screening interval for prostatecancer based on prostate-specific antigen level: results of a prospective, randomized,population-based study. Arch Intern Med,2005,165(16):1857-1861.
[25] Nam RK, Zhang WW, Trachtenberg J, et al. Utility of incorporating genetic variants forthe early detection of prostate cancer. Clin Cancer Res,2009,15(5):1787-1793.
[26] Mistry K and Cable G. Meta-analysis of prostate-specific antigen and digital rectalexamination as screening tests for prostate carcinoma. J Am Board Fam Pract,2003,16(2):95-101.
[27] Thompson IM, Ankerst DP, Chi C, et al. Assessing prostate cancer risk: results from theProstate Cancer Prevention Trial. J Natl Cancer Inst,2006,98(8):529-534.
[28] Lin DW. Beyond PSA: utility of novel tumor markers in the setting of elevated PSA.Urol Oncol,2009,27(3):315-321.
[29] Steineck G, Helgesen F, Adolfsson J, et al. Quality of life after radical prostatectomy orwatchful waiting. N Engl J Med,2002,347(11):790-796.
[30] Litwin MS, Gore JL, Kwan L, et al. Quality of life after surgery, external beamirradiation, or brachytherapy for early-stage prostate cancer. Cancer,2007,109(11):2239-2247.
[31] Barry MJ. Screening for prostate cancer--the controversy that refuses to die. N Engl JMed,2009,360(13):1351-1354.
[32] Goessl C, Krause H, Muller M, et al. Fluorescent methylation-specific polymerase chainreaction for DNA-based detection of prostate cancer in bodily fluids. Cancer Res,2000,60(21):5941-5945.
[33] Hoque MO, Topaloglu O, Begum S, et al. Quantitative methylation-specific polymerasechain reaction gene patterns in urine sediment distinguish prostate cancer patients fromcontrol subjects. J Clin Oncol,2005,23(27):6569-6575.
[34] Roupret M, Hupertan V, Yates DR, et al. Molecular detection of localized prostatecancer using quantitative methylation-specific PCR on urinary cells obtained followingprostate massage. Clin Cancer Res,2007,13(6):1720-1725.
[35] Laxman B, Tomlins SA, Mehra R, et al. Noninvasive detection of TMPRSS2:ERGfusion transcripts in the urine of men with prostate cancer. Neoplasia,2006,8(10):885-888.
[36] Demichelis F, Fall K, Perner S, et al. TMPRSS2:ERG gene fusion associated with lethalprostate cancer in a watchful waiting cohort. Oncogene,2007,26(31):4596-4599.
[37] Thuret R, Chantrel-Groussard K, Azzouzi AR, et al. Clinical relevance of geneticinstability in prostatic cells obtained by prostatic massage in early prostate cancer. Br JCancer,2005,92(2):236-240.
[38] Sun J, Zheng SL, Wiklund F, et al. Sequence variants at22q13are associated withprostate cancer risk. Cancer Res,2009,69(1):10-15.
[39] Hsu FC, Sun J, Wiklund F, et al. A novel prostate cancer susceptibility locus at19q13.Cancer Res,2009,69(7):2720-2723.
[40] Mikolajczyk SD, Grauer LS, Millar LS, et al. A precursor form of PSA (pPSA) is acomponent of the free PSA in prostate cancer serum. Urology,1997,50(5):710-714.
[41] Mikolajczyk SD, Millar LS, Wang TJ, et al."BPSA," a specific molecular form of freeprostate-specific antigen, is found predominantly in the transition zone of patients withnodular benign prostatic hyperplasia. Urology,2000,55(1):41-45.
[42] Mikolajczyk SD, Marks LS, Partin AW, et al. Free prostate-specific antigen in serum isbecoming more complex. Urology,2002,59(6):797-802.
[43] Recker F, Kwiatkowski MK, Piironen T, et al. Human glandular kallikrein as a tool toimprove discrimination of poorly differentiated and non-organ-confined prostate cancercompared with prostate-specific antigen. Urology,2000,55(4):481-485.
[44] Luo J, Zha S, Gage WR, et al. Alpha-methylacyl-CoA racemase: a new molecularmarker for prostate cancer. Cancer Res,2002,62(8):2220-2226.
[45]王科峰,吴斌.脂肪酸合成酶与前列腺癌.中华男科学杂志,2008,14(8):740-742.
[46] Mhawech-Fauceglia P, Zhang S, Terracciano L, et al. Prostate-specific membraneantigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivityand specificity in prostate adenocarcinoma: an immunohistochemical study usingmutiple tumour tissue microarray technique. Histopathology,2007,50(4):472-483.
[47]郎根强,孙颖浩,许传亮,等.前列腺癌组织中前列腺干细胞抗原的表达及其意义.临床泌尿外科杂志,2003,18(1):27-29.
[48] Paul B, Dhir R, Landsittel D, et al. Detection of prostate cancer with a blood-basedassay for early prostate cancer antigen. Cancer Res,2005,65(10):4097-4100.
[49] Voloshyna I, Besana A, Castillo M, et al. TREK-1is a novel molecular target in prostatecancer. Cancer Res,2008,68(4):1197-1203.
[50] Wang X, Yu J, Sreekumar A, et al. Autoantibody signatures in prostate cancer. N Engl JMed,2005,353(12):1224-1235.
[51] Bussemakers MJ, van Bokhoven A, Verhaegh GW, et al. DD3: a new prostate-specificgene, highly overexpressed in prostate cancer. Cancer Res,1999,59(23):5975-5879.
[52]陈占国,陈伟,陶志华,等.基因测序筛选前列腺癌患者PCA3(DD3)基因外显子多态性.中国男科学杂志,2009,23(11):10-13.
[53] de Kok JB, Verhaegh GW, Roelofs RW, et al. DD3(PCA3), a very sensitive and specificmarker to detect prostate tumors. Cancer Res,2002,62(9):2695-2698.
[54] Jung M, Xu C, Spethmann J, et al. Re: Hessels D, Klein Gunnewiek JMT, van Oort I,Karthaus HFM, van Leenders GJL, van Balken B, Kiemeney LA, Witjes JA, SchalkenJA. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. EurUrol2003;44:8-16. Eur Urol,2004,46(2):271-272.
[55] Hessels D, Klein Gunnewiek JM, van Oort I, et al. DD3(PCA3)-based molecular urineanalysis for the diagnosis of prostate cancer. Eur Urol,2003,44(1):8-15; discussion15-16.
[56] Fradet Y, Saad F, Aprikian A, et al. uPM3, a new molecular urine test for the detectionof prostate cancer. Urology,2004,64(2):311-315; discussion315-316.
[57] Groskopf J, Aubin SM, Deras IL, et al. APTIMA PCA3molecular urine test:development of a method to aid in the diagnosis of prostate cancer. Clin Chem,2006,52(6):1089-1095.
[58] Nyberg M, Ulmert D, Lindgren A, et al. PCA3as a diagnostic marker for prostatecancer: a validation study on a Swedish patient population. Scand J Urol Nephrol,2010,44(6):378-383.
[59] Shen M, Chen W, Yu K, et al. The diagnostic value of PCA3gene-based analysis ofurine sediments after digital rectal examination for prostate cancer in a Chinesepopulation. Exp Mol Pathol,2011,90(1):97-100.
[60] Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer amongmen with a prostate-specific antigen level
[62] Pepe P, Fraggetta F, Galia A, et al. PCA3score and prostate cancer diagnosis at repeatedsaturation biopsy. Which cut-off:20or35? Int Braz J Urol,2012,38(4):489-495.
[63] Augustin H, Mayrhofer K, Pummer K, et al. Relationship between prostate cancer gene3(PCA3) and characteristics of tumor aggressiveness. Prostate,2013,73(2):203-210.
[64] van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, et al. Detailed analysis ofhistopathological parameters in radical prostatectomy specimens and PCA3urine testresults. Prostate,2008,68(11):1215-1222.
[65] Haese A, de la Taille A, van Poppel H, et al. Clinical utility of the PCA3urine assay inEuropean men scheduled for repeat biopsy. Eur Urol,2008,54(5):1081-1088.
[66] Nakanishi H, Groskopf J, Fritsche HA, et al. PCA3molecular urine assay correlateswith prostate cancer tumor volume: implication in selecting candidates for activesurveillance. J Urol,2008,179(5):1804-1809; discussion1809-1810.
[67]刘光香,郭宏骞,李笑弓,等. PCA3在前列腺癌患者前列腺按摩后尿液中的表达.现代泌尿外科杂志,2009,14(1):18-21.
[68] Klatte T, Waldert M, de Martino M, et al. Age-specific PCA3score reference values fordiagnosis of prostate cancer. World J Urol,2012,30(3):405-410.
[69] Tombal B, Andriole GL, de la Taille A, et al. Clinical judgment versus biomarkerprostate cancer gene3: which is best when determining the need for repeat prostatebiopsy? Urology,2013,81(5):998-1004.
[70] Tinzl M, Marberger M, Horvath S, et al. DD3PCA3RNA analysis in urine--a newperspective for detecting prostate cancer. Eur Urol,2004,46(2):182-186; discussion187.
[71] van Gils MP, Hessels D, van Hooij O, et al. The time-resolved fluorescence-basedPCA3test on urinary sediments after digital rectal examination; a Dutch multicentervalidation of the diagnostic performance. Clin Cancer Res,2007,13(3):939-943.
[72] Marks LS, Fradet Y, Deras IL, et al. PCA3molecular urine assay for prostate cancer inmen undergoing repeat biopsy. Urology,2007,69(3):532-535.
[73] Hessels D and Schalken JA. The use of PCA3in the diagnosis of prostate cancer. NatRev Urol,2009,6(5):255-261.
[74] van Gils MP, Cornel EB, Hessels D, et al. Molecular PCA3diagnostics on prostaticfluid. Prostate,2007,67(8):881-887.
[75] Fontenete S, Silva J, Teixeira AL, et al. Controversies in using urine samples forProstate Cancer detection: PSA and PCA3expression analysis. Int Braz J Urol,2011,37(6):719-726.
[76] Thomas CE, Sexton W, Benson K, et al. Urine collection and processing for proteinbiomarker discovery and quantification. Cancer Epidemiol Biomarkers Prev,2010,19(4):953-959.
[77] Medeiros M, Sharma VK, Ding R, et al. Optimization of RNA yield, purity and mRNAcopy number by treatment of urine cell pellets with RNAlater. J Immunol Methods,2003,279(1-2):135-142.
[78] Tichopad A, Didier A and Pfaffl MW. Inhibition of real-time RT-PCR quantification dueto tissue-specific contaminants. Mol Cell Probes,2004,18(1):45-50.
[79] Batura D and Gopal Rao G. The national burden of infections after prostate biopsy inEngland and Wales: a wake-up call for better prevention--authors' response. JAntimicrob Chemother,2013,68(10):2419-2420.
[80] Ramos CG, Valdevenito R, Vergara I, et al. PCA3sensitivity and specificity for prostatecancer detection in patients with abnormal PSA and/or suspicious digital rectalexamination. First Latin American experience. Urol Oncol,2013,31(8):1522-1526.
[81] Ochiai A, Okihara K, Kamoi K, et al. Clinical utility of the prostate cancer gene3(PCA3) urine assay in Japanese men undergoing prostate biopsy. BJU Int,2013,111(6):928-933.
[82] Capoluongo E, Zambon CF, Basso D, et al. PCA3score of20could improve prostatecancer detection: results obtained on734Italian individuals. Clin Chim Acta,2014,429:46-50.·[83] Salagierski M, Mulders P and Schalken JA. Predicting prostate biopsy outcome using aPCA3-based nomogram in a Polish cohort. Anticancer Res,2013,33(2):553-557.
[84] van Bokhoven A, Varella-Garcia M, Korch C, et al. Molecular characterization ofhuman prostate carcinoma cell lines. Prostate,2003,57(3):205-225.
[85] Landers KA, Burger MJ, Tebay MA, et al. Use of multiple biomarkers for a moleculardiagnosis of prostate cancer. Int J Cancer,2005.114(6):950-956.
[86]陶志华,毛晓露,王彩虹,等. DD3mRNA在前列腺癌组织中定量表达分析.中华男科学杂志,2007,13(2):130-133.
[87] Meng FJ, Shan A, Jin L, et al. The expression of a variant prostate-specific antigen inhuman prostate. Cancer Epidemiol Biomarkers Prev,2002,11(3):305-309.
[88] Shappell SB, Fulmer J, Arguello D, et al. PCA3urine mRNA testing for prostatecarcinoma: patterns of use by community urologists and assay performance in referencelaboratory setting. Urology,2009,73(2):363-368.
[89] Wang R, Chinnaiyan AM, Dunn RL, et al. Rational approach to implementation ofprostate cancer antigen3into clinical care. Cancer,2009,115(17):3879-3886.
[90] Ng CF, Yeung R, Chiu PK, et al. The role of urine prostate cancer antigen3mRNAlevels in the diagnosis of prostate cancer among Hong Kong Chinese patients. HongKong Med J,2012,18(6):459-465.
[91] Crawford ED, Rove KO, Trabulsi EJ, et al. Diagnostic performance of PCA3to detectprostate cancer in men with increased prostate specific antigen: a prospective study of1,962cases. J Urol,2012,188(5):1726-1731.
[92] Chevli KK, Duff M, Walter P, et al. Urinary PCA3as a Predictor of Prostate Cancer in aCohort of3,073Men Undergoing Initial Prostate Biopsy. J Urol,2013.
[93] Marks LS and Bostwick DG. Prostate Cancer Specificity of PCA3Gene Testing:Examples from Clinical Practice. Rev Urol,2008,10(3):175-181.
[94] Ruffion A, Devonec M, Champetier D, et al. PCA3and PCA3-based nomogramsimprove diagnostic accuracy in patients undergoing first prostate biopsy. Int J Mol Sci,2013,14(9):17767-17780.