【作者】 郑晨曦；

【导师】 戴起宝； 陈绍勤；

【作者基本信息】 福建医科大学 ， 肿瘤学， 2009， 硕士

【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。更多还原

【Abstract】 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.更多还原