TGFβ、HNF4α在原发性肝癌中的表达及临床意义

Expression of TGFβ and HNF4α in hepatocellular carcinoma and their significance on clinicopathologic features

目的研究TGFβ和HNF4α在肝癌及癌旁组织中的表达,探讨其在肝癌发生、发展中的作用和意义。方法采用qRT-PCR和Western blotting方法检测54例原发性肝癌患者肝癌及对应癌旁组织中TGFβ和HNF4αmRNA及蛋白表达水平;免疫组化检测所有肝癌组织中TGFβ和HNF4α蛋白的表达水平,统计学分析两者与肝癌患者临床病理特征的关系。结果 (1)与癌旁组织比,TGFβmRNA在肝癌组织中表达升高[(0.294±0.142)vs(0.231±0.149),P=0.020];HNF4αmRNA在肝癌组织中表达降低[(0.104±0.130 vs(0.151±0.079),P=0.037];(2)Western blotting结果显示:与癌旁组织比,TGFβ蛋白在肝癌组织中高表达[(0.224±0.060)vs(0.051±0.019),P=0.025],HNF4α蛋白在肝癌组织中表达下降[(0.103±0.033)vs(0.315±0.024),P=0.017];(3)免疫组化检测显示,肝癌组织中TGFβ蛋白阳性表达率66.7%,HNF4α蛋白阳性表达率为57.4%。在肝癌组织中TGFβ蛋白表达水平与肿瘤分化(χ~2=4.339,P=0.037)及TNM分期(χ~2=4.488,P=0.034)相关;HNF4α蛋白与肿瘤分化(χ~2=5.032,P=0.025)相关。TGFβ蛋白与HNF4α蛋白呈负相关(r=-0.291,P=0.033)。结论 TGFβ和HNF4α基因相互调控EMT进程,参与原发性肝癌的发生发展。

Objective To investigate the correlation and clinical significance of transforming growth factorβ(TGFβ)and hepatocyte nuclear factor4α(HNF4α)in human hepatocellular carcinoma(HCC).Methods The mRNA and protein expression of TGFβand HNF4αwere detected by qRT-PCR,Western blotting and immunohistochemistry methods in54HCC tissues and corresponding adjacent cancer tissues.The correlation of protein expression of TGFβand HNF4αin HCC with clinicopathological features were analyzed statistically.Results(1)Compared with the adjacent cancer tissues,the expression of TGFβmRNA in HCC tissues was significantly increased[(0.294±0.142)vs(0.231±0.149),P=0.020];the expression of HNF4αmRNA in HCC tissues was significantly decreased[(0.104±0.130)vs(0.151±0.079),P=0.037];(2)Western blotting results showed that,compared with the adjacent cancer tissues,the levels of TGFβprotein in HCC tissues increased in HCC tissues[(0.224±0.060)vs(0.051±0.019),P=0.025].The expression of HNF4αprotein decreased in HCC tissues[(0.103±0.033)vs(0.315±0.024),P=0.017];(3)Immunohistochemistry results showed that,the positive expression rate of TGFβprotein was66.7%,and the positive expression rate of HNF4αprotein was57.4%in HCC tissues.TGFβprotein expression was correlated to tumor differentiation(χ2=4.339,P=0.037)and TNM stage(χ2=4.488,P=0.034).HNF4αprotein expression was correlated with tumor differentiation(χ2=5.032,P=0.025).TGFβprotein expression was negatively correlated with HNF4αprotein expression(r=-0.291,P=0.033).Conclusion Our study suggests that the TGFβand HNF4αgenes may involve in the development of HCC via epithelial to mesenchymal transition regulation.