α_1-抗胰蛋白酶、转铁蛋白、PRO2619在胆管癌中的表达及意义
|
摘要
目的:检测α1-抗胰蛋白酶(AAT)、转铁蛋白(TF)、PRO2619在胆管癌组织中的表达情况和AAT、TF在胆管癌患者外周血清中的表达情况,以进一步验证本课题组前期应用双向凝胶电泳-质谱技术分离胆管癌患者血清蛋白的研究结果,探讨这些肿瘤相关蛋白与胆管癌发生发展的关系,以期寻找新的有效的肿瘤标志物,提高胆管癌的早期诊断水平。
方法:应用免疫组织化学S-P法检测42例胆管癌组织和19例正常胆管组织石蜡标本中AAT、TF及PRO2619蛋白的表达水平。同时应用免疫散射比浊法测定20例胆管癌患者及10例胆管结石患者术前血清中AAT和TF水平,并对比AAT、TF与传统肿瘤标志物CEA、CA19-9在诊断胆管癌的应用情况。
结果:
1、AAT、TF、PRO2619在胆管癌组织和正常胆管组织中的表达:AAT在胆管癌组织和正常胆管组织中表达阳性率分别为83.3%和47.4%,二者差异有统计学意义(P<0.05);TF在胆管癌组织和正常胆管组织中表达阳性率分别为47.6%和57.9%,二者差异无统计学意义(P>0.05);PRO2619在胆管癌组织和正常胆管组织中表达阳性率分别为40.5%和78.9%,二者差异有统计学意义(P<0.05)。
2、AAT在胆管癌组织中的表达水平与胆管癌临床病理特征的关系:AAT表达水平与患者的性别、年龄、肿瘤部位、淋巴结转移之间的关系均无统计学意义(P>0.05),而与胆管癌分化程度、周围浸润及UICC分期之间的关系均有统计学意义(P<0.05)。
3、TF在胆管癌组织中的表达水平与胆管癌临床病理特征的关系:TF表达水平与患者的性别、年龄、肿瘤部位、分化程度、淋巴结转移、周围浸润及UICC分期之间的关系均无统计学意义(P>0.05)。
4、PRO2619在胆管癌组织中的表达水平与胆管癌临床病理特征的关系: PRO2619表达水平与患者的性别、年龄、肿瘤部位、淋巴结转移、周围浸润及UICC分期之间的关系均无统计学意义(P>0.05),而与胆管癌分化程度之间的关系有统计学意义(P<0.05)。
5、AAT、TF、PRO2619在胆管癌组织中表达的相关性:胆管癌中AAT与TF的表达无相关(r=0.17,P>0.05),AAT与PRO2619的表达无相关(r=0.24,P>0.05),TF与PRO2619的表达无相关(r=-0.01,P>0.05)。
6、AAT、TF在外周血清中测定值:胆管癌患者AAT值为2.60±0.53g/L,胆管结石患者AAT值为1.71±0.35g/L,二者差异有统计学意义(P<0.05);胆管癌患者TF值为1.98±0.48g/L,胆管结石患者TF值为2.46±0.23g/L,二者差异有统计学意义(P<0.05)。
7、胆管癌血清中AAT、TF值的异常率与CA19-9、CEA值的异常率的比较:胆管癌患者中AAT、TF、CA19-9、CEA值的异常率分别为80%、60%、75%、45%。AAT值的异常率与CA19-9比较,二者差异没有统计学意义(P>0.05);AAT值的异常率与CEA比较,二者差异有统计学意义(P<0.05);TF值的异常率分别与CA19-9、CEA比较,均无统计学意义(P>0.05)。
结论:
1、AAT在胆管癌组织表达程度明显高于正常胆管组织,但随着胆管癌分化程度的降低、周围组织的浸润及UICC分期的增加而表达降低,提示AAT可能与胆管癌的恶性演进过程关系密切。
2、TF在胆管癌组织与正常胆管组织表达程度无明显差别,且与患者的性别、年龄、肿瘤部位、分化程度、淋巴结转移、周围浸润及UICC分期之间的关系无关。
3、PRO2619在胆管癌组织表达程度明显低于正常胆管组织,且随着胆管癌分化程度的降低而表达降低,提示PRO2619的变化可能与胆管癌的恶性程度有关。
4、AAT在胆管癌患者外周血清中测定值明显高于胆管结石患者,其异常率与CA19-9比较差异无统计学意义,与CEA比较差异有统计学意义,提示AAT可作为一项与CA19-9作用相似的肿瘤标志物来监测胆管癌的发生。
5、TF在胆管癌患者外周血清中测定值明显低于胆管结石患者,但其异常率与CA19-9异常率、CEA异常率比较均无统计学意义,提示TF在外周血清中的降低可能伴随着胆管癌的发生发展。
Objective: Detection ofα1-antitrypsin(AAT), transferrin(TF), PRO2619 in cholangiocarcinoma tissues and AAT, TF in peripheral blood of patients with cholangiocarcinoma in the expression of clearance, to further validate the application of the pre-group two-dimensional gel electrophoresis-mass spectrometry separation of serum proteins in patients with bile duct cancer research findings, discussion of these tumor-associated protein and the relationship between the occurrence and development of cholangiocarcinoma, with a view to looking for new and effective marker of tumor, improve the level of the early diagnosis of cholangiocarcinoma. Methods: SP immunohistochemical method assay 42 cases of cholangiocarcinoma and 19 cases of bile duct carcinoma paraffin specimens to expression the protein level of AAT, TF and PRO2619, the application of immune nephelometry method and 20 cases of cholangiocarcinoma in patients with 10 cases of bile duct stones in patients with preoperative serum levels of AAT and TF, and contrast AAT, TF with traditional tumor markers CEA, CA19-9 in the diagnosis of cholangiocarcinoma application.
Results:
1. AAT, TF, PRO2619 in the bile duct cholangiocarcinoma and normal tissues: AAT in the bile duct cholangiocarcinoma and normal tissues positive rates were 83.3% and 47.4%, the difference has statistical significance (P<0.05); TF in the bile duct cholangiocarcinoma and normal tissues positive rates were 47.6% and 57.9%, the difference was not significant (P>0.05); PRO2619 in the duct cholangiocarcinoma and normal tissues positive rates were 40.5% and 78.9%, the difference has statistical significance (P<0.05).
2. AAT in cholangiocarcinoma and cholangiocarcinoma of the expression level of the relationship between clinicopathological features: AAT expression in cholangiocarcinoma levels had no statistically significant relationship between patient's sex, age, tumor site, lymph node metastasis(P<0.05), with cholangiocarcinoma differentiation, around the infiltration and UICC staging, the relationship between the statistical are significance (P<0.05).
3. TF in cholangiocarcinoma and cholangiocarcinoma of the expression level of the relationship between clinicopathological features: TF expression in cholangiocarcinoma levels had no statistically significant relationship between patient's sex, age, tumor location, differentiation degree, lymph node metastasis, around the infiltration and UICC staging(P>0.05).
4. PRO2619 in cholangiocarcinoma and cholangiocarcinoma of the expression level of the relationship between clinicopathological features: PRO2619 expression in cholangiocarcinoma had no statistically significant relationship between patient's sex, age, tumor site, lymph node metastasis, around the infiltration and UICC staging(P>0.05),there is statistical significance with cholangiocarcinoma of the relationship between the degree of differentiation(P<0.05).
5. AAT, TF, PRO2619 expression in cholangiocarcinoma relevance: AAT and TF expression in the cholangiocarcinoma was no correlation(r=0.17, P>0.05),AAT expression with no correlation with PRO2619(r=0.24, P>0.05),TF expression and no correlation with PRO2619(r=-0.01, P>0.05).
6. AAT, TF measured in the peripheral blood-money value: the value of AAT in serum of patients with cholangiocarcinoma are 2.60±0.53g/L, serum of patients with bile duct stones in the value of AAT are 1.71±0.35g/L,there were significant differences between the two(P<0.05); the value of TF in serum of patients with cholangiocarcinoma are 1.98±0.48g/L, serum of patients with bile duct stones in the value of TF are 2.46±0.23g/L, there were significant differences between the two(P<0.05).
7. Compared the rate of abnormal about AAT, TF values and CA19-9, CEA values in cholangiocarcinoma serum: cholangiocarcinoma in patients with AAT, TF, CA19-9, CEA values were abnormal rate of 80%, 60%, 75%, 45%. AAT value of the abnormal rate compared with CA19-9, the difference is not statistically significant(P>0.05); the abnormal rate of AAT value compared with the CEA,the abnormal, the difference has statistical significance(P <0.05); the abnormal rate of TF value compared with CA19-9, CEA, there were no statistical significance(P>0.05).
Conclusions:
1. AAT expression in cholangiocarcinoma was significantly higher than normal degree of bile duct organization, but with cholangiocarcinoma of the lower degree of differentiation, invasion of surrounding tissue and increase in stages UICC expression, AAT may be associated with cholangiocarcinoma prompted vicious close evolutionary process.
2. TF in cholangiocarcinoma tissue and normal tissue expression of the degree of bile duct was no significant difference, and with the patient's sex, age, tumor location, differentiation degree, lymph node metastasis, UICC staging around the infiltration and the relationship between the non-relevance.
3. PRO2619 at the level of bile duct carcinoma tissues was significantly higher than that of normal bile duct organization, but differentiation of bile duct cancer with lower levels of expression, PRO2619 probably prompted changes in the vicious and the degree of bile duct cancer.
4. AAT clearance at peripheral blood of patients with cholangiocarcinoma was significantly higher than that measured in patients with bile duct stones, the abnormal rate of CA19-9 was no significant difference compared with the CEA has statistically significant difference, AAT can be used as a prompt and CA19-9 is similar to the role of tumor markers to monitor the occurrence of cholangiocarcinoma.
5. TF in the peripheral blood of patients with cholangiocarcinoma was significantly lower than that measured in patients with bile duct stones, but the abnormal rate and the rate of CA19-9 abnormality, CEA abnormality rates were not statistically significance, suggesting that TF in the peripheral blood may be accompanied by the decrease in the occurrence and development of cholangiocarcinoma.
方法:应用免疫组织化学S-P法检测42例胆管癌组织和19例正常胆管组织石蜡标本中AAT、TF及PRO2619蛋白的表达水平。同时应用免疫散射比浊法测定20例胆管癌患者及10例胆管结石患者术前血清中AAT和TF水平,并对比AAT、TF与传统肿瘤标志物CEA、CA19-9在诊断胆管癌的应用情况。
结果:
1、AAT、TF、PRO2619在胆管癌组织和正常胆管组织中的表达:AAT在胆管癌组织和正常胆管组织中表达阳性率分别为83.3%和47.4%,二者差异有统计学意义(P<0.05);TF在胆管癌组织和正常胆管组织中表达阳性率分别为47.6%和57.9%,二者差异无统计学意义(P>0.05);PRO2619在胆管癌组织和正常胆管组织中表达阳性率分别为40.5%和78.9%,二者差异有统计学意义(P<0.05)。
2、AAT在胆管癌组织中的表达水平与胆管癌临床病理特征的关系:AAT表达水平与患者的性别、年龄、肿瘤部位、淋巴结转移之间的关系均无统计学意义(P>0.05),而与胆管癌分化程度、周围浸润及UICC分期之间的关系均有统计学意义(P<0.05)。
3、TF在胆管癌组织中的表达水平与胆管癌临床病理特征的关系:TF表达水平与患者的性别、年龄、肿瘤部位、分化程度、淋巴结转移、周围浸润及UICC分期之间的关系均无统计学意义(P>0.05)。
4、PRO2619在胆管癌组织中的表达水平与胆管癌临床病理特征的关系: PRO2619表达水平与患者的性别、年龄、肿瘤部位、淋巴结转移、周围浸润及UICC分期之间的关系均无统计学意义(P>0.05),而与胆管癌分化程度之间的关系有统计学意义(P<0.05)。
5、AAT、TF、PRO2619在胆管癌组织中表达的相关性:胆管癌中AAT与TF的表达无相关(r=0.17,P>0.05),AAT与PRO2619的表达无相关(r=0.24,P>0.05),TF与PRO2619的表达无相关(r=-0.01,P>0.05)。
6、AAT、TF在外周血清中测定值:胆管癌患者AAT值为2.60±0.53g/L,胆管结石患者AAT值为1.71±0.35g/L,二者差异有统计学意义(P<0.05);胆管癌患者TF值为1.98±0.48g/L,胆管结石患者TF值为2.46±0.23g/L,二者差异有统计学意义(P<0.05)。
7、胆管癌血清中AAT、TF值的异常率与CA19-9、CEA值的异常率的比较:胆管癌患者中AAT、TF、CA19-9、CEA值的异常率分别为80%、60%、75%、45%。AAT值的异常率与CA19-9比较,二者差异没有统计学意义(P>0.05);AAT值的异常率与CEA比较,二者差异有统计学意义(P<0.05);TF值的异常率分别与CA19-9、CEA比较,均无统计学意义(P>0.05)。
结论:
1、AAT在胆管癌组织表达程度明显高于正常胆管组织,但随着胆管癌分化程度的降低、周围组织的浸润及UICC分期的增加而表达降低,提示AAT可能与胆管癌的恶性演进过程关系密切。
2、TF在胆管癌组织与正常胆管组织表达程度无明显差别,且与患者的性别、年龄、肿瘤部位、分化程度、淋巴结转移、周围浸润及UICC分期之间的关系无关。
3、PRO2619在胆管癌组织表达程度明显低于正常胆管组织,且随着胆管癌分化程度的降低而表达降低,提示PRO2619的变化可能与胆管癌的恶性程度有关。
4、AAT在胆管癌患者外周血清中测定值明显高于胆管结石患者,其异常率与CA19-9比较差异无统计学意义,与CEA比较差异有统计学意义,提示AAT可作为一项与CA19-9作用相似的肿瘤标志物来监测胆管癌的发生。
5、TF在胆管癌患者外周血清中测定值明显低于胆管结石患者,但其异常率与CA19-9异常率、CEA异常率比较均无统计学意义,提示TF在外周血清中的降低可能伴随着胆管癌的发生发展。
Objective: Detection ofα1-antitrypsin(AAT), transferrin(TF), PRO2619 in cholangiocarcinoma tissues and AAT, TF in peripheral blood of patients with cholangiocarcinoma in the expression of clearance, to further validate the application of the pre-group two-dimensional gel electrophoresis-mass spectrometry separation of serum proteins in patients with bile duct cancer research findings, discussion of these tumor-associated protein and the relationship between the occurrence and development of cholangiocarcinoma, with a view to looking for new and effective marker of tumor, improve the level of the early diagnosis of cholangiocarcinoma. Methods: SP immunohistochemical method assay 42 cases of cholangiocarcinoma and 19 cases of bile duct carcinoma paraffin specimens to expression the protein level of AAT, TF and PRO2619, the application of immune nephelometry method and 20 cases of cholangiocarcinoma in patients with 10 cases of bile duct stones in patients with preoperative serum levels of AAT and TF, and contrast AAT, TF with traditional tumor markers CEA, CA19-9 in the diagnosis of cholangiocarcinoma application.
Results:
1. AAT, TF, PRO2619 in the bile duct cholangiocarcinoma and normal tissues: AAT in the bile duct cholangiocarcinoma and normal tissues positive rates were 83.3% and 47.4%, the difference has statistical significance (P<0.05); TF in the bile duct cholangiocarcinoma and normal tissues positive rates were 47.6% and 57.9%, the difference was not significant (P>0.05); PRO2619 in the duct cholangiocarcinoma and normal tissues positive rates were 40.5% and 78.9%, the difference has statistical significance (P<0.05).
2. AAT in cholangiocarcinoma and cholangiocarcinoma of the expression level of the relationship between clinicopathological features: AAT expression in cholangiocarcinoma levels had no statistically significant relationship between patient's sex, age, tumor site, lymph node metastasis(P<0.05), with cholangiocarcinoma differentiation, around the infiltration and UICC staging, the relationship between the statistical are significance (P<0.05).
3. TF in cholangiocarcinoma and cholangiocarcinoma of the expression level of the relationship between clinicopathological features: TF expression in cholangiocarcinoma levels had no statistically significant relationship between patient's sex, age, tumor location, differentiation degree, lymph node metastasis, around the infiltration and UICC staging(P>0.05).
4. PRO2619 in cholangiocarcinoma and cholangiocarcinoma of the expression level of the relationship between clinicopathological features: PRO2619 expression in cholangiocarcinoma had no statistically significant relationship between patient's sex, age, tumor site, lymph node metastasis, around the infiltration and UICC staging(P>0.05),there is statistical significance with cholangiocarcinoma of the relationship between the degree of differentiation(P<0.05).
5. AAT, TF, PRO2619 expression in cholangiocarcinoma relevance: AAT and TF expression in the cholangiocarcinoma was no correlation(r=0.17, P>0.05),AAT expression with no correlation with PRO2619(r=0.24, P>0.05),TF expression and no correlation with PRO2619(r=-0.01, P>0.05).
6. AAT, TF measured in the peripheral blood-money value: the value of AAT in serum of patients with cholangiocarcinoma are 2.60±0.53g/L, serum of patients with bile duct stones in the value of AAT are 1.71±0.35g/L,there were significant differences between the two(P<0.05); the value of TF in serum of patients with cholangiocarcinoma are 1.98±0.48g/L, serum of patients with bile duct stones in the value of TF are 2.46±0.23g/L, there were significant differences between the two(P<0.05).
7. Compared the rate of abnormal about AAT, TF values and CA19-9, CEA values in cholangiocarcinoma serum: cholangiocarcinoma in patients with AAT, TF, CA19-9, CEA values were abnormal rate of 80%, 60%, 75%, 45%. AAT value of the abnormal rate compared with CA19-9, the difference is not statistically significant(P>0.05); the abnormal rate of AAT value compared with the CEA,the abnormal, the difference has statistical significance(P <0.05); the abnormal rate of TF value compared with CA19-9, CEA, there were no statistical significance(P>0.05).
Conclusions:
1. AAT expression in cholangiocarcinoma was significantly higher than normal degree of bile duct organization, but with cholangiocarcinoma of the lower degree of differentiation, invasion of surrounding tissue and increase in stages UICC expression, AAT may be associated with cholangiocarcinoma prompted vicious close evolutionary process.
2. TF in cholangiocarcinoma tissue and normal tissue expression of the degree of bile duct was no significant difference, and with the patient's sex, age, tumor location, differentiation degree, lymph node metastasis, UICC staging around the infiltration and the relationship between the non-relevance.
3. PRO2619 at the level of bile duct carcinoma tissues was significantly higher than that of normal bile duct organization, but differentiation of bile duct cancer with lower levels of expression, PRO2619 probably prompted changes in the vicious and the degree of bile duct cancer.
4. AAT clearance at peripheral blood of patients with cholangiocarcinoma was significantly higher than that measured in patients with bile duct stones, the abnormal rate of CA19-9 was no significant difference compared with the CEA has statistically significant difference, AAT can be used as a prompt and CA19-9 is similar to the role of tumor markers to monitor the occurrence of cholangiocarcinoma.
5. TF in the peripheral blood of patients with cholangiocarcinoma was significantly lower than that measured in patients with bile duct stones, but the abnormal rate and the rate of CA19-9 abnormality, CEA abnormality rates were not statistically significance, suggesting that TF in the peripheral blood may be accompanied by the decrease in the occurrence and development of cholangiocarcinoma.
引文
[1]黄洁夫,陈积圣,邹声泉,等.胆管癌的病因、病理及临床表现[J].肝脏胆道肿瘤外科学,1999,44(1):709-712.
[2]杨尽晖,蒋波,吴金术,等.肿瘤标志物CEA、CA19-9联合检测在胆管癌诊治中的价值[J].中国医师杂志,2005,7(4):552-553.
[3]熊俊,郑启昌,胡俊华,等.肿瘤标志物CA19-9和CA242联合检测在胆管癌中的诊断价值[J].肝胆外科杂志,2005,13(3):203-205.
[4]孙浩,罗文军,吴晓春,等.联合检测CEA、CA19-9、CA50的对老年胆管癌的诊断价值[J].重庆医科大学学报,2007,32(3):287-289.
[5] Aroni K, Kittas C, Papadimitriou CS, et al. An immunocytochemical study of the distribution of lysozyme,α1-antitrypsin and a1-antichymotrypsin in the normal and pathological gall bladder[J]. Virchows Arch A Pathol Anat Histopathol. 1984, 403(3): 281-289.
[6] De SáSV, Corrêa-Giannella ML, Machado MC, et al. Serpin peptidase inhibitor clade A member 1 as a potential marker for malignancy in insulinomas[J]. Clin Cancer Res. 2007, 13(18 Pt 1): 5322-5330.
[7] Magro G, Perissinotto D, Schiappacassi M, et al. Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas[J]. Am J Pathol. 2003 , 163(1): 183-196.
[8] Chahed K, Kabbage M, Ehret-Sabatier L, et al. Expression of fibrinogen E-fragment and fibrin E-fragment is inhibited in the human infiltrating ductal carcinoma of the breast: the two-dimensional electrophoresis and MALDI-TOF-mass spectrometry analyses [J]. Int J Oncol. 2005 , 27(5): 1425-1431.
[9]黄立军,王云杰,张志培,等.α1-抗胰蛋白酶在非小细胞肺癌组织中表达的意义[J].现代肿瘤医学,2005,13(1):7-9.
[10]崔行,王鑫,于清水,等.血清α1-抗胰蛋白酶检测对多种恶性肿瘤的诊断价值[J].肿瘤防治研究,1997,24(1):13-15.
[11] Klein CE, Ozer HL, Traganos F, et al. A transformation-associated 130-kD cellsurface glycoprotein is growth controlled in normal human cells[J]. J Exp Med.1988, 167(5): 1684-1696.
[12] Huber M, Limat A, Wagner E, et al. Efficient in vitro transfection of human keratinocytes with an adenovirus-enhanced receptor-mediated system[J]. J Invest Dermatol. 2000, 114(4): 661-666.
[13] Yuan X, Russell T, Wood G, et al. Analysis of the human lumbar cerebrospinal fluid proteome [J]. Electrophoresis. 2002, 23(7-8): 1185-1196.
[14]郑丰平,袁世珍,冯智英,等.TSP、VEGF与大肠癌血管生成、转移关系的研究[J].实用肿瘤杂志,2000,15(6):394-395.
[15]周宁新,刘永雄,黄志强,等.肝外胆管癌全国调查1098例分析[J].中华外科杂志,1990,28(9):516-521.
[16] Wasinger VC, Cordewell SJ, Cerpa-Poljak A, et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis, 1995, 16(7): 1090-1094.
[17] Rai AJ, Zhang z, Rosenzweig J, et a1. Proteomic approaches to tumor marker discovery [J]. Arch Pathol Lab Med, 2002, 126(12): 1518-1526.
[18] Lawrie LC, Fothergill JE, Murray GI. Spot the differences: proteomics in cancer research[J]. Lancet Oncol, 2001, 2(5): 270-277.
[19] Srisomsap C, Sawangareetrakul P, Subhasitanont P, et a1. Proteomic analysis of cholangiocarcinoma cell line[J]. Proteomics, 2004, 4(4): 1135-44.
[20] Kristiansen TZ, Bunkenborg J, Gronborg M, et al. A Proteomic Analysis of Human Bile[J]. Mol Cell Proteomics, 2004, 3(4): 715-728.
[21] Eriksson S. Pulmonar emphysema andα1-antitrypsin deficieney [J]. Acta Med Scnad, 1964, 175: 197-205.
[22] Gadek JE, Klein HG, Holland PV, et al. G.Replacement therapy of alpha l-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects [J]. J Clin Invest, 1981, 68(5): 1158-1165.
[23] Eriksson S, Hagerstrand I. Cirrhosis and malignant hepatoma inα1-antitrypsin deficiency [J]. Acta Med Scand, 1974, 195(6): 451-458.
[24] Doustjalali SR, Yusof R, Yip CH, et al. Aberrant expression of acute-phasereactant proteins in sera and breast lesions of patients with malignant and benign breast tumors [J]. Electrophoresis, 2004, 25(14): 2392-2401.
[25] Zelvyte I, Lindgren S, Janciauskiene S. Multiple effects of alphal-antitrypsin on breast carcinoma MDA-MB 468 cell growth and invasiveness [J]. Eur J Cancer Prev, 2003, 12(2): 117-124.
[26] Guner G, Kirkali G, Baskin Y, et al. Elastase levels in small and non-smallcell lung carcinoma [J]. Biochem Soc Trans, 1993, 12(2): 305-305.
[27] Nejjari M, Berthet V, Rigot V, et al. Inhibition of proprotein convertases enhances cell migration and metastases development of human colon carcinoma cells in a rat model[J]. Am J Pathol, 2004, 164(6): 1925-1933.
[28] Lee K, Kye M, Jang JS, et al. Proteomic analysis revealed a strong association of a high level of alphal-antitrypsin in gastric juice with gastric cancer [J]. Proteomics,2004, 4(11): 3343-3352.
[29] Schwartz AG, Rothrock M, Yang P, et al. Increased cancer risk among relatives of nonsmoking lung cancer cases[J]. Genet Epidemiol.1999, 17(1): l-15.
[30] Schwart AG. Genetic predisposition to lung cancer[J]. Chest, 2004, 125(5): 86S-89S.
[31] Geiger B, Bershadsky A, Pankov R, et al. Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk [J]. Nat Rev Mol Cell Biol, 2001, 2(11): 793-805.
[32] D,Agostino P, Camemi AR, Caruso R, et al. Matrix metalloproteinases production in malignant pleural effusions after talc pleurodesis [J]. Clin Exp Immunol, 2003, 134(l): 138-142.
[33] Perlmutter, DH, Cole FS, et al. Expression of the a1-proteinase inhibitor gene in human monocytes and macrophages[J]. Proc Natl Acad Sci USA, 1985, 82(3): 795-799.
[34] Molmenti EP, Perlmutter DH, Rubin DC. Cell-specific expression of alpha 1-antitrypsin in human intestinal epithelium[J]. J Clin Invest, 1993, 92(4): 2022-2034.
[35] Venembre P, Boutten A, Seta N, et al. Secretion of alpha1-antitrypsin by alveolar epithelial cells [J]. FEBS Lett, 1994, 346(2-3): 171-174.
[36]李定国,阎兰.α1-抗胰蛋白酶异质体的检测及其诊断价值[J].中华医学检验杂志,1990,13(3):141-141.
[37] Moy LS, Howe K, Moy RL. Glycolic acid modulation of collagen production in human skin fibroblast cultures in vitro [J]. Dermatol Surg 1996, 22(5): 439-441.
[38]陈勇,戴和平,龙志高,等.人皮肤成纤维细胞的分离和体外培养[J].湖南医科大学学报,2002,27(5):25-25.
[39] Setzen G. Willams EFⅢ. Tissue response to uture materials implanted subcutaneously in a rabbit model [J]. Plast Reconstr Surg. 1997, 100(7): 1788-1795.
[40] Klein AW. Indications and implantation techniques for the various formulations of injectable collagen [J]. Dermatol Surg Oncol. 1998, 24(11): 27-31.
[41] Lemperle G, Hazan-Gairthier N, Lempperle M. PMMA-microspheres (Artecoll) for long-lasting correction of wrinkles: refinements and statistical results[J]. Aesthetic Plast Surg. 1998, 22(5): 356-365.
[42] Baumann LS, Kerdel F. The treatment of bovine collagen allergy with cyclosporin [J]. J Dermal Surg, 1999, 25(3): 247-249.
[43] Klein AW. Know all your options for soft tissue augmentation [J]. Skin and Aging, 1999, 7(2): 66-69.
[44] Kuo T, Speyer MT, Ries RW, et al. Collagen thermal damage and collagen synthesis after cutaneous laser therapy[J]. Lasers Surg Med, 1998, 23(2): 66-71.
[45]于慧敏,乔惠珍.皮肤成纤维细胞培养的改良法[J].中国优生与遗传杂志,1999,7(3):72-72.
[46] Sugio S, Kashima A, Mochizuki S, et al. Crystal structure of human serum albumin at 2.5 A resolution[J]. Protein Eng, 1999, 12, (6): 439-446.
[1] Wasinger VC, Cordewell SJ, Cerpa-Poljak A, et al. Progress with geneproduct mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis, 1995, 16(7): 1090-1094.
[2] Rai AJ, Zhang z, Rosenzweig J, et a1. Proteomic approaches to tumor marker discovery [J]. Arch Pathol Lab Med, 2002, 126(12): 1518-1526.
[3] Lawrie LC, Fothergill JE, Murray GI. Spot the differences:proteomics in cancer research[J]. Lancet Oncol, 2001, 2(5): 270-277.
[4] Emmert Buck MR, Gillespie JW, Paweletz CP, et al. An approach to Proteomic analysis of human tumors[J]. Mol Carcinog, 2000, 27(3): 158-165.
[5] Grace MP, Kim KH, True LD, et al. Keratin expression in normal esophageal epithelium and squamous cell carcinoma of the esophagus[J]. Cancer Res, 1985, 45(2): 841-846.
[6] Doak SH, Jenkins GJ, Parry EM, et al. Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett’s oesophagus - their association with aneuploidy and neoplastic progression[J]. Mutat Res, 2004, 547(1-2): 133-144.
[7] An JY, Fan ZM, Zhuang Zh, et al. Proteomic analysis of blood level of proteins before and after operation in patients with esophageal squamous cell carcinoma at high-incidence area in Henan Province[J]. World J Gastroenterol, 2004, 10(22): 3365-3368.
[8] Wang KJ, Wang RT, Zhang JZ. Identification of tumor markers using two-dimensional electrophoresis in gastric carcinoma[J]. WorId J Gastroenterol, 2004, 10(15): 2179-2183.
[9] Ryu JW, Kim HJ, Lee YS, et al. The proteomics approach to find biomakers in gastric cancer[J]. J Korean Med Sci, 2003, 18(4): 505-509.
[10] Sinha P, Poland J, Schnolzer M, et al. Characterization of the differential protein expression associated with thermoresistance in human gastric carcinoma cell lines[J]. Electrophoresis, 2001, 22(14): 2990-3000.
[11] Kim J, Kim SH, Lee SU, et al. Proteome analysis of human liver tumor tissue by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of disease- related proteins[J]. Electrophoresis, 2002, 23(24): 4142-4156.
[12] Le Naour F, Brichory F, Misek DE, et a l. A d istinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic anal-ysis[J]. Mol Cell Proteomics, 2002, 1(3): 197-203.
[13] Poon TC, Yip TT, Chan AT, et al. Comprehensive Proteomic Profiling Identifies Serum Porteomic Signatuers for Detection of Hepatocellular Carcinoma and Its Subtypes[J]. Clin Chem, 2003, 49(5): 752-760.
[14] Srisomsap C, Sawangareetrakul P, Subhasitanont P, et a1. Proteomic analysis of cholangiocarcinoma cell line[J]. Proteomics, 2004, 4(4): 1135-1144.
[15] Kristiansen TZ, Bunkenborg J, Gronborg M, et al. A Proteomic Analysis of Human Bile[J]. Mol Cell Proteomics, 2004, 3(4): 715-728.
[16] Imamura T, Kanai F, Kawakami T, et al. Proteomic analysis of the TGF - beta signaling pathway in pancreatic carcinoma cells using stable RNA interference to silence Smad4 expression[J]. Biochem Biophys Res Commun, 2004, 318(1): 289-296.
[17] Shekouh AR, Thompson CC, Prime W, et al. Application of laser ca- Pture microdissection combined with two - dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma[J]. Proteomics, 2003, 3(10): 1988-2001.
[18] Bi X, Lin Q, Foo TW, et a1. Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways:mechanism of tumorigenesis[J]. Mol Cell Proteomics, 2006, 5(6): lll9-ll30.
[19] Brunagel G, Schoen RE, Bauer AJ, et a1. Nuclear matrix protein alterations associated with colon cancer metastasis to the liver[J]. Clin Cancer Res, 2002, 8 (10): 3039-3045.
[20]陈益定,郑树,余捷凯,等.血清蛋白质质谱模型在大肠癌诊断中的应用[J].中华肿瘤杂志,2004,26(7):417-420.
[21] Stierum R, Gaspari M, Dommels Y, et a1. Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2[J]. Biochim Biophys Acta, 2003, 650(1-2): 73-91.
[2]杨尽晖,蒋波,吴金术,等.肿瘤标志物CEA、CA19-9联合检测在胆管癌诊治中的价值[J].中国医师杂志,2005,7(4):552-553.
[3]熊俊,郑启昌,胡俊华,等.肿瘤标志物CA19-9和CA242联合检测在胆管癌中的诊断价值[J].肝胆外科杂志,2005,13(3):203-205.
[4]孙浩,罗文军,吴晓春,等.联合检测CEA、CA19-9、CA50的对老年胆管癌的诊断价值[J].重庆医科大学学报,2007,32(3):287-289.
[5] Aroni K, Kittas C, Papadimitriou CS, et al. An immunocytochemical study of the distribution of lysozyme,α1-antitrypsin and a1-antichymotrypsin in the normal and pathological gall bladder[J]. Virchows Arch A Pathol Anat Histopathol. 1984, 403(3): 281-289.
[6] De SáSV, Corrêa-Giannella ML, Machado MC, et al. Serpin peptidase inhibitor clade A member 1 as a potential marker for malignancy in insulinomas[J]. Clin Cancer Res. 2007, 13(18 Pt 1): 5322-5330.
[7] Magro G, Perissinotto D, Schiappacassi M, et al. Proteomic and postproteomic characterization of keratan sulfate-glycanated isoforms of thyroglobulin and transferrin uniquely elaborated by papillary thyroid carcinomas[J]. Am J Pathol. 2003 , 163(1): 183-196.
[8] Chahed K, Kabbage M, Ehret-Sabatier L, et al. Expression of fibrinogen E-fragment and fibrin E-fragment is inhibited in the human infiltrating ductal carcinoma of the breast: the two-dimensional electrophoresis and MALDI-TOF-mass spectrometry analyses [J]. Int J Oncol. 2005 , 27(5): 1425-1431.
[9]黄立军,王云杰,张志培,等.α1-抗胰蛋白酶在非小细胞肺癌组织中表达的意义[J].现代肿瘤医学,2005,13(1):7-9.
[10]崔行,王鑫,于清水,等.血清α1-抗胰蛋白酶检测对多种恶性肿瘤的诊断价值[J].肿瘤防治研究,1997,24(1):13-15.
[11] Klein CE, Ozer HL, Traganos F, et al. A transformation-associated 130-kD cellsurface glycoprotein is growth controlled in normal human cells[J]. J Exp Med.1988, 167(5): 1684-1696.
[12] Huber M, Limat A, Wagner E, et al. Efficient in vitro transfection of human keratinocytes with an adenovirus-enhanced receptor-mediated system[J]. J Invest Dermatol. 2000, 114(4): 661-666.
[13] Yuan X, Russell T, Wood G, et al. Analysis of the human lumbar cerebrospinal fluid proteome [J]. Electrophoresis. 2002, 23(7-8): 1185-1196.
[14]郑丰平,袁世珍,冯智英,等.TSP、VEGF与大肠癌血管生成、转移关系的研究[J].实用肿瘤杂志,2000,15(6):394-395.
[15]周宁新,刘永雄,黄志强,等.肝外胆管癌全国调查1098例分析[J].中华外科杂志,1990,28(9):516-521.
[16] Wasinger VC, Cordewell SJ, Cerpa-Poljak A, et al. Progress with gene-product mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis, 1995, 16(7): 1090-1094.
[17] Rai AJ, Zhang z, Rosenzweig J, et a1. Proteomic approaches to tumor marker discovery [J]. Arch Pathol Lab Med, 2002, 126(12): 1518-1526.
[18] Lawrie LC, Fothergill JE, Murray GI. Spot the differences: proteomics in cancer research[J]. Lancet Oncol, 2001, 2(5): 270-277.
[19] Srisomsap C, Sawangareetrakul P, Subhasitanont P, et a1. Proteomic analysis of cholangiocarcinoma cell line[J]. Proteomics, 2004, 4(4): 1135-44.
[20] Kristiansen TZ, Bunkenborg J, Gronborg M, et al. A Proteomic Analysis of Human Bile[J]. Mol Cell Proteomics, 2004, 3(4): 715-728.
[21] Eriksson S. Pulmonar emphysema andα1-antitrypsin deficieney [J]. Acta Med Scnad, 1964, 175: 197-205.
[22] Gadek JE, Klein HG, Holland PV, et al. G.Replacement therapy of alpha l-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects [J]. J Clin Invest, 1981, 68(5): 1158-1165.
[23] Eriksson S, Hagerstrand I. Cirrhosis and malignant hepatoma inα1-antitrypsin deficiency [J]. Acta Med Scand, 1974, 195(6): 451-458.
[24] Doustjalali SR, Yusof R, Yip CH, et al. Aberrant expression of acute-phasereactant proteins in sera and breast lesions of patients with malignant and benign breast tumors [J]. Electrophoresis, 2004, 25(14): 2392-2401.
[25] Zelvyte I, Lindgren S, Janciauskiene S. Multiple effects of alphal-antitrypsin on breast carcinoma MDA-MB 468 cell growth and invasiveness [J]. Eur J Cancer Prev, 2003, 12(2): 117-124.
[26] Guner G, Kirkali G, Baskin Y, et al. Elastase levels in small and non-smallcell lung carcinoma [J]. Biochem Soc Trans, 1993, 12(2): 305-305.
[27] Nejjari M, Berthet V, Rigot V, et al. Inhibition of proprotein convertases enhances cell migration and metastases development of human colon carcinoma cells in a rat model[J]. Am J Pathol, 2004, 164(6): 1925-1933.
[28] Lee K, Kye M, Jang JS, et al. Proteomic analysis revealed a strong association of a high level of alphal-antitrypsin in gastric juice with gastric cancer [J]. Proteomics,2004, 4(11): 3343-3352.
[29] Schwartz AG, Rothrock M, Yang P, et al. Increased cancer risk among relatives of nonsmoking lung cancer cases[J]. Genet Epidemiol.1999, 17(1): l-15.
[30] Schwart AG. Genetic predisposition to lung cancer[J]. Chest, 2004, 125(5): 86S-89S.
[31] Geiger B, Bershadsky A, Pankov R, et al. Transmembrane crosstalk between the extracellular matrix-cytoskeleton crosstalk [J]. Nat Rev Mol Cell Biol, 2001, 2(11): 793-805.
[32] D,Agostino P, Camemi AR, Caruso R, et al. Matrix metalloproteinases production in malignant pleural effusions after talc pleurodesis [J]. Clin Exp Immunol, 2003, 134(l): 138-142.
[33] Perlmutter, DH, Cole FS, et al. Expression of the a1-proteinase inhibitor gene in human monocytes and macrophages[J]. Proc Natl Acad Sci USA, 1985, 82(3): 795-799.
[34] Molmenti EP, Perlmutter DH, Rubin DC. Cell-specific expression of alpha 1-antitrypsin in human intestinal epithelium[J]. J Clin Invest, 1993, 92(4): 2022-2034.
[35] Venembre P, Boutten A, Seta N, et al. Secretion of alpha1-antitrypsin by alveolar epithelial cells [J]. FEBS Lett, 1994, 346(2-3): 171-174.
[36]李定国,阎兰.α1-抗胰蛋白酶异质体的检测及其诊断价值[J].中华医学检验杂志,1990,13(3):141-141.
[37] Moy LS, Howe K, Moy RL. Glycolic acid modulation of collagen production in human skin fibroblast cultures in vitro [J]. Dermatol Surg 1996, 22(5): 439-441.
[38]陈勇,戴和平,龙志高,等.人皮肤成纤维细胞的分离和体外培养[J].湖南医科大学学报,2002,27(5):25-25.
[39] Setzen G. Willams EFⅢ. Tissue response to uture materials implanted subcutaneously in a rabbit model [J]. Plast Reconstr Surg. 1997, 100(7): 1788-1795.
[40] Klein AW. Indications and implantation techniques for the various formulations of injectable collagen [J]. Dermatol Surg Oncol. 1998, 24(11): 27-31.
[41] Lemperle G, Hazan-Gairthier N, Lempperle M. PMMA-microspheres (Artecoll) for long-lasting correction of wrinkles: refinements and statistical results[J]. Aesthetic Plast Surg. 1998, 22(5): 356-365.
[42] Baumann LS, Kerdel F. The treatment of bovine collagen allergy with cyclosporin [J]. J Dermal Surg, 1999, 25(3): 247-249.
[43] Klein AW. Know all your options for soft tissue augmentation [J]. Skin and Aging, 1999, 7(2): 66-69.
[44] Kuo T, Speyer MT, Ries RW, et al. Collagen thermal damage and collagen synthesis after cutaneous laser therapy[J]. Lasers Surg Med, 1998, 23(2): 66-71.
[45]于慧敏,乔惠珍.皮肤成纤维细胞培养的改良法[J].中国优生与遗传杂志,1999,7(3):72-72.
[46] Sugio S, Kashima A, Mochizuki S, et al. Crystal structure of human serum albumin at 2.5 A resolution[J]. Protein Eng, 1999, 12, (6): 439-446.
[1] Wasinger VC, Cordewell SJ, Cerpa-Poljak A, et al. Progress with geneproduct mapping of the Mollicutes: Mycoplasma genitalium[J]. Electrophoresis, 1995, 16(7): 1090-1094.
[2] Rai AJ, Zhang z, Rosenzweig J, et a1. Proteomic approaches to tumor marker discovery [J]. Arch Pathol Lab Med, 2002, 126(12): 1518-1526.
[3] Lawrie LC, Fothergill JE, Murray GI. Spot the differences:proteomics in cancer research[J]. Lancet Oncol, 2001, 2(5): 270-277.
[4] Emmert Buck MR, Gillespie JW, Paweletz CP, et al. An approach to Proteomic analysis of human tumors[J]. Mol Carcinog, 2000, 27(3): 158-165.
[5] Grace MP, Kim KH, True LD, et al. Keratin expression in normal esophageal epithelium and squamous cell carcinoma of the esophagus[J]. Cancer Res, 1985, 45(2): 841-846.
[6] Doak SH, Jenkins GJ, Parry EM, et al. Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett’s oesophagus - their association with aneuploidy and neoplastic progression[J]. Mutat Res, 2004, 547(1-2): 133-144.
[7] An JY, Fan ZM, Zhuang Zh, et al. Proteomic analysis of blood level of proteins before and after operation in patients with esophageal squamous cell carcinoma at high-incidence area in Henan Province[J]. World J Gastroenterol, 2004, 10(22): 3365-3368.
[8] Wang KJ, Wang RT, Zhang JZ. Identification of tumor markers using two-dimensional electrophoresis in gastric carcinoma[J]. WorId J Gastroenterol, 2004, 10(15): 2179-2183.
[9] Ryu JW, Kim HJ, Lee YS, et al. The proteomics approach to find biomakers in gastric cancer[J]. J Korean Med Sci, 2003, 18(4): 505-509.
[10] Sinha P, Poland J, Schnolzer M, et al. Characterization of the differential protein expression associated with thermoresistance in human gastric carcinoma cell lines[J]. Electrophoresis, 2001, 22(14): 2990-3000.
[11] Kim J, Kim SH, Lee SU, et al. Proteome analysis of human liver tumor tissue by two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-mass spectrometry for identification of disease- related proteins[J]. Electrophoresis, 2002, 23(24): 4142-4156.
[12] Le Naour F, Brichory F, Misek DE, et a l. A d istinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic anal-ysis[J]. Mol Cell Proteomics, 2002, 1(3): 197-203.
[13] Poon TC, Yip TT, Chan AT, et al. Comprehensive Proteomic Profiling Identifies Serum Porteomic Signatuers for Detection of Hepatocellular Carcinoma and Its Subtypes[J]. Clin Chem, 2003, 49(5): 752-760.
[14] Srisomsap C, Sawangareetrakul P, Subhasitanont P, et a1. Proteomic analysis of cholangiocarcinoma cell line[J]. Proteomics, 2004, 4(4): 1135-1144.
[15] Kristiansen TZ, Bunkenborg J, Gronborg M, et al. A Proteomic Analysis of Human Bile[J]. Mol Cell Proteomics, 2004, 3(4): 715-728.
[16] Imamura T, Kanai F, Kawakami T, et al. Proteomic analysis of the TGF - beta signaling pathway in pancreatic carcinoma cells using stable RNA interference to silence Smad4 expression[J]. Biochem Biophys Res Commun, 2004, 318(1): 289-296.
[17] Shekouh AR, Thompson CC, Prime W, et al. Application of laser ca- Pture microdissection combined with two - dimensional electrophoresis for the discovery of differentially regulated proteins in pancreatic ductal adenocarcinoma[J]. Proteomics, 2003, 3(10): 1988-2001.
[18] Bi X, Lin Q, Foo TW, et a1. Proteomic analysis of colorectal cancer reveals alterations in metabolic pathways:mechanism of tumorigenesis[J]. Mol Cell Proteomics, 2006, 5(6): lll9-ll30.
[19] Brunagel G, Schoen RE, Bauer AJ, et a1. Nuclear matrix protein alterations associated with colon cancer metastasis to the liver[J]. Clin Cancer Res, 2002, 8 (10): 3039-3045.
[20]陈益定,郑树,余捷凯,等.血清蛋白质质谱模型在大肠癌诊断中的应用[J].中华肿瘤杂志,2004,26(7):417-420.
[21] Stierum R, Gaspari M, Dommels Y, et a1. Proteome analysis reveals novel proteins associated with proliferation and differentiation of the colorectal cancer cell line Caco-2[J]. Biochim Biophys Acta, 2003, 650(1-2): 73-91.