TGFβ1与Smad4基因在肝细胞癌中的表达及意义

Expression of TGFβ1 and Smad4 gene in human hepatocellular carcinoma tissues and its significance

目的:通过检测TGFβ1与Smad4基因在肝细胞癌(HCC)中的表达,初步探讨TGFβ/Smad信号通路中TGFβ1与Co-Smad(Smad4)与HCC的发生、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HCC组织切片中癌与癌旁TGFβ1、Smad4蛋白、Smad4 mRNA的表达,5例外伤性肝破裂手术切除标本作正常对照。比较HCC组与对照组及HCC癌组织与癌旁组织TGFβ1与Smad4蛋白、Smad4 mRNA表达的差异。结果:正常对照组TGFβ1呈阴性表达,Smad4蛋白、Smad4 mRNA均呈阳性表达;TGFβ1在HCC组织中阳性表达率为78.0%(32/41),在癌旁组织中为95.1%(39/41),两者比较差异显著(P<0.05);Smad4蛋白在HCC组织中阳性表达率为48.8%(20/41),在癌旁组织中为78.0%(32/41),两者比较有显著差异(P<0.01);Smad4 mRNA在HCC组织中阳性表达率为51.2%(21/41),在癌旁组织中为73.1%(30/41),两者比较有显著差异(P<0.05);与正常肝组织比较,HCC组织中Smad4蛋白和Smad4 mRNA阳性表达均显著降低(P<0.05);Smad4 mRNA在HCC组织中阳性表达在病理分级Ⅰ、Ⅱ级与Ⅲ、Ⅳ级之间存在显著差异(P<0.05),Ⅲ、Ⅳ级阳性表达较Ⅰ、Ⅱ级降低;癌旁组织中Smad4蛋白的阳性面积百分比、吸光度及Smad4 mRNA的阳性面积百分比均显著高于HCC组织中(P<0.05)。HCC中Smad4蛋白、Smad4 mRNA与TGFβ1比较均存在显著差异(P<0.05),但均无显著相关性(P>0.05)。结论:TGFβ1过表达、Smad4表达缺失可能在HCC的发生、发展中发挥重要作用。

Objective：To investigate the correlation of TGFβ1, Smad4 genes with carcinogenesis and tumor progression of human hepatocellular carcinoma（HCC）. Methods ： IHC and ISH method were used to detect the expression of TGFβ1, Smad4 gene in 41 cases of HCC and adjacent noncancer liver tissues （ANLT）. Results：The expression of TGFβ1 in normal liver tissues was negative, but the expression of Smad4, Smad4 mRNA was positive. The positive expression of TGFβ1 ,Smad4 and Smad4 mRNA was detected in 32 cases（78.0%）,20 cases（48.8%） and 21 cases（51.2%）, respectively, for 41 cases of HCC; 39 cases（95.1%）, 32 cases （78.0%） and 30 cases（73. 1% ） for the corresponding 41 cases of ANLT. The expression lever of TGFβ1 ,in ANLT of HCC was significantly higher than those of in HCC tissues （ P 〈 0. 05 ）. The expression lever of Smad4,as the same as Smad4 mRNA,in HCC tissues was significantly lower than those of in ANLT of HCC （ P 〈 0. 05 ）. The expression of Smad4 mRNA in HCC tissues was significantly lower in Ⅲ-Ⅳ pathological grades than in Ⅰ -Ⅱ pathological grades（P 〈0. 05）. Smad4 and Smad4 mRNA were not correlated to age and sex. Conclusion：The over-expression of TGFβ1 and the lower-expression of Smad4 genes may play an important role in occurrence and progression of HCC.