肝细胞癌中CYP3A43表达及其预后价值

Correlation between CYP3A43 expression and its prognosis predictive value in hepatocellular carcinoma

目的 探讨CYP3A43在肝细胞癌(肝癌)及正常肝组织中的表达水平,分析其与患者预后生存的相关性。方法 分析Gene Expression Omnibus(GEO,GSE14520)和The Cancer Genome Atlas(TCGA)中肝细胞癌及癌旁组织高通量表达数据,确定CYP3A43在肝癌与癌旁组织中mRNA水平表达差异,及其与患者预后的关系;通过对107例肝癌组织样本和20例正常肝组织样本进行免疫组化检测,比较CYP3A43蛋白水平表达差异,分析肝癌组织中CYP3A43蛋白水平表达与患者临床病例参数和预后的关系。结果 对GEO和TCGA数据的分析显示mRNA水平CYP3A43的表达在肝癌显著下调(相对癌旁非癌组织);免疫组化结果证实肝癌组织中蛋白水平CYP3A43表达相对正常肝组织显著下调,并提示CYP3A43低表达患者肿瘤分化较差;Kaplan-Meier生存分析显示肝癌组织中mRNA和蛋白水平CYP3A43低表达均与患者不良预后相关;Cox回归分析显示CYP3A43低表达是患者预后的独立风险因素。结论 肝癌组织中CYP3A43表达下调,且CYP3A43低表达与肝癌细胞低分化相关,是患者预后不良的独立危险因素。

Objective To investigate the expression level of CYP3A43 in hepatocellular carcinoma(HCC)and normal liver tissue,and to analyze whether CYP3A43 expression in HCC tissue correlates with the prognosis of HCC patients.Methods TCGA and GEO(GSE14520)data were analyzed to determine CYP3A43 mRNA expression level and prognostic value.We performed immunohistochemical(IHC)assays in 107 HCC and 20 normal liver tissue samples to compare CYP3A43 protein expression difference between normal liver and HCC tissues,and to analyze the clinical and prognostic value of CYP3A43 protein expression in HCC tissues.Results The data from GEO and TCGA suggested that,compared with that in adjacent non-tumor tissue,CYP3A43 mRNA was significantly down regulated in HCC tissue.IHC assays further confirmed that CYP3A43 protein was down regulated in HCC tissue.Kaplan-Meier analysis indicated that both the mRNA and protein levels of down regulated CYP3A43 expression in HCC tissue correlated with the poor prognosis of HCC patients.In addition,analysis also indicated that low CYP3A43 expression in HCC tissue associated with poor differentiation of HCC(P<0.05).Conclusion Compared with that in adjacent non-tumor and normal liver tissue,CYP3A43 expression is significantly down-regulated in HCC tissue.Low CYP3A43 expression correlates with poor tumor differentiation,and indicates the poor prognosis of HCC patients.