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目的:拟通过检测Smad4基因在肝细胞癌(HCC)中的表达,初步探讨TGFβ-Smad信号通路中Co-Smad(Smad4)与肝细胞癌的发生和发展之间的可能关系。方法:采用免疫组化ABC法及原位杂交法(ISH)检测41例肝细胞癌组织切片中癌与癌旁Smad4蛋白和mRNA的表达,5例外伤性肝破裂手术切除标本作为正常对照。比较HCC组与对照组及HCC与癌旁Smad4蛋白和mRNA表达的差异,并进行统计分析。结果:正常对照组Smad4蛋白和mRNA均呈阳性表达;HCC组织Smad4蛋白阳性率为48.8%(20/41),癌旁组织中为78.0%(32/41),两者比较差异有统计学意义,P<0.01;HCC组织Smad4mRNA阳性率为51.2%(21/41),癌旁组织中为73.1%(30/41),两者比较差异有统计学意义,P<0.05;与正常肝组织比较,HCC组织中Smad4蛋白和mRNA阳性表达均显著降低,P<0.05;HCC组织Smad4mRNA阳性表达在病理分级Ⅰ、Ⅱ级与Ⅲ、Ⅳ级之间差异有统计学意义,P<0.05。结论:Smad4基因表达缺失可能在肝细胞癌的发生和发展中发挥作用。
Objective: To investigate the possible relationship between Co-Smad (Smad4) and the occurrence and development of hepatocellular carcinoma in TGFβ-Smad signaling pathway by detecting the expression of Smad4 in hepatocellular carcinoma (HCC). Methods: Immunohistochemical ABC method and in situ hybridization (ISH) were used to detect the expression of Smad4 protein and mRNA in 41 cases of hepatocellular carcinoma and 5 cases of traumatic hepatic rupture as normal control. The differences of protein and mRNA expression of Smad4 between HCC group and control group, HCC and adjacent cancer tissues were compared and statistically analyzed. Results: The positive expression of Smad4 protein and mRNA in normal control group was positive. The positive rate of Smad4 protein in HCC tissues was 48.8% (20/41) and that in paracancerous tissues was 78.0% (32/41), the difference was statistically significant , P <0.01. The positive rates of Smad4 mRNA in HCC tissues were 51.2% (21/41) and 73.1% (30/41) in paracancerous tissues, respectively, with significant difference between the two groups (P <0.05) , The positive expression of Smad4 protein and mRNA in HCC tissues were significantly decreased, P <0.05; the positive expression of Smad4 mRNA in HCC tissues was significantly different between pathological grade Ⅰ, Ⅱ and Ⅲ, Ⅳ, P <0.05. Conclusion: The loss of Smad4 gene expression may play a role in the occurrence and development of hepatocellular carcinoma.