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Claudin-1和Claudin-10在肝细胞癌中的表达及意义

Expression and Significance of Claudin-1 and Claudin-10 in Human Hepatocellular Carcinoma

【作者】 张正东

【导师】 耿小平;

【作者基本信息】 安徽医科大学 , 外科学, 2011, 硕士

【摘要】 目的:研究紧密连接蛋白Claudin-1和Claudin-10在肝细胞癌(hepatocellar carcinoma、HCC)组织、癌旁组织和正常肝组织中的表达情况,探讨Claudin-1和Claudin-10表达与HCC发生及其预后的关系。方法:采用实时荧光定量PCR(qRT-PCR)检测35例肝癌组织及相应癌旁组织和10例正常肝组织中Claudin-1和Claudin-10mRNA的表达水平,同时用免疫组化SP(Streptavidin-perosidase)法技术检测35例肝癌组织及其相应癌旁组织中Claudin-1和Claudin-10蛋白的表达情况。结果:Claudin-1 mRNA在肝癌组织中的表达明显低于癌旁组织及正常肝组织,差异有统计学意义(P<0.05);而癌旁组织与正常肝组织比较,差异无统计学意义(P>0.05);Claudin-1 mRNA的表达与HCC患者性别、年龄、AFP表达水平、HBsAg、病理分化程度、包膜完整性、门静脉癌栓形成、肿瘤个数及肿瘤大小无关(P>0.05),与患者术后一年无瘤生存率无关(P>0.05)。HCC组织及癌旁组织中均有Claudin-1蛋白表达,其阳性表达率分别为65.7%和88.6%。Claudin-1蛋白表达于阳性细胞胞质及胞膜上;Claudin-1蛋白在HCC组织中的表达显著低于癌旁组织(P<0.05);Claudin-1蛋白表达与HCC患者性别、年龄、肿瘤个数、AFP表达水平、HBsAg、包膜完整性及肿瘤大小无关(P>0.05),与患者术后一年无瘤生存率无关(P>0.05);而与肝癌病理分化程度及门脉癌栓形成相关(P<0.05)。Claudin-10 mRNA在肝癌组织中的表达明显高于癌旁组织及正常肝组织,差异有统计学意义(P<0.05);而癌旁组织与正常肝组织比较,差异无统计学意义(P>0.05);Claudin-10 mRNA的表达与HCC患者性别、年龄、AFP表达水平、HBsAg、病理分化程度、包膜完整性、门静脉癌栓形成、肿瘤个数及肿瘤大小无关(P>0.05),与患者术后一年无瘤生存率无关(P>0.05)。HCC组织及癌旁组织中均有Claudin-10蛋白表达,其阳性表达率分别为60%和22.9%。Claudin-10蛋白表达于阳性细胞胞质及胞膜上;Claudin-10蛋白在HCC组织中的表达显著高于癌旁组织(P<0.05);Claudin-10蛋白表达与HCC患者性别、年龄、肿瘤个数、AFP表达水平、HBsAg、包膜完整性及肿瘤大小无关(P>0.05),与患者术后一年无瘤生存率无关(P>0.05);而与肝癌病理分化程度及门脉癌栓形成相关(P<0.05)。结论:Claudin-1和Claudin-10与HCC的发生、浸润和转移有关;Claudin-1和Claudin-10可作为HCC发生、发展的预测指标之一。

【Abstract】 Objective: To detect the expression of Claudin-1and Claudin-10 in the HCC tissues ,paracarcinomatous tissues and normal liver tissues and explore their relationships with the oncogenesis and prognosis of HCC.Methods: Fluorescence and real-time quantitative PCR were carried out to detect the level of Claudin-1and Claudin-10 mRNA from 35 hepatocellar carcinoma tissues and their corresponding normal tissues and 10 normal liver tissues,and the expression of Claudin-1 and Claudin-10 protein were detected by immunohistochemical SP method in 35 hepatocellar carcinoma tissues and their corresponding normal tissues.Results: Lower expression of Claudin-1 mRNA was found in hepatocellar carcinoma tissues,compared with that in their corresponding normal tissues (P<0.05),but not between paracarcinomatous tissues and normal liver tissues (P>0.05). The level of Claudin-1mRNA expression in hepatocellar carcinoma was not significantly correlated with sex,age,AFP levels,HBsAg,pathological types, the integrity of tumor capsule,Portal vein tumor thrombus,tumor number and tumor size (P>0.05).and the expression of Claudin-1 mRNA in HCC tissues has no correlation with the One-year disease-free survival of patients (P>0.05). The expression of Claudin-1 protein was observed in HCC tissues and paracarcinomatous tissues,The positive rate of Claudin-1 protein were 65.7%,88.6%respectively. The brown granules of positive cell were mainly distributed in the cytoplasm and cell membrane. The expression of Claudin-1 protein in HCC tissues was significantly lower than that in the paracarcinomatous tissues (P<0.05). Claudin-1 protein expression were not related to sex,age,tumor number,AFP levels,HBsAg,the integrity of tumor capsule and tumor size (P>0.05),and has no correlation with the One-year disease-free survival of patients (P>0.05). But were significantly correlated with pathological differentiation of HCC,Portal vein tumor thrombus (P<0.05).Higher expression of Claudin-10 mRNA was found in hepatocellar carcinoma tissues,compared with that in their corresponding normal tissues (P<0.05),but not between paracarcinomatous tissues and normal liver tissues (P>0.05).The level of Claudin-10 mRNA expression in hepatocellar carcinoma was not significantly correlated with sex,age,AFP levels,HBsAg,pathological types,the integrity of tumor capsule,portal vein tumor thrombus,tumor number and tumor size (P>0.05). and the expression of Claudin-10 mRNA in HCC tissues has no correlation with the One-year disease-free survival of patients (P>0.05). The expression of Claudin-10 protein was observed in HCC tissues and paracarcinomatous tissues,the positive rate of Claudin-10 protein were 60%,22.9%respectively. The brown granules of positive cell were mainly distributed in the cytoplasm and cell membrane. The expression of Claudin-10 protein in HCC tissues was significantly higher than that in the paracarcinomatous tissues (P<0.05). Claudin-1 protein expression were not related to sex,age,tumor number,AFP levels,HBsAg,the integrity of tumor capsule and tumor size (P>0.05),and has no correlation with the One-year disease-free survival of patients (P>0.05). But were significantly correlated with pathological differentiation of HCC,portal vein tumor thrombus (P<0.05).Conclusion: Claudin-1and Claudin-10 are related to the carcinogenesis,infiltration and metastasis of HCC,the level of Claudin-1and Claudin-10 expression might be a valuable marker for diagnosis and prognosis of HCC.

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