结直肠癌C-erbB-2基因启动子CpG岛甲基化状态及其与C-erbB-2蛋白表达的关系

目的了解结直肠癌组织C-erbB-2基因启动子区CpG岛甲基化状态、C-erbB-2蛋白表达水平及两者之间的关系。方法取经病理确诊的43例结直肠癌组织和相应癌旁组织,分别用甲基化特异性聚合酶链反应(MSP)和免疫组织化学法(IHC)检测C-erbB-2启动子区CpG岛的甲基化和C-erbB-2蛋白表达水平。结果癌组织和癌旁组织中C-erbB-2启动子区CpG岛甲基化率分别为44.2%和74.4%,差异具有统计学意义(P=0.004)。癌组织和癌旁组织中C-erbB-2蛋白过度表达率分别为67.4%和27.9%,差异具有统计学意义(P=0.000)。C-erbB-2蛋白表达水平与肿瘤分期相关。结直肠癌组织C-erbB-2启动子区CpG岛甲基化状态与C-erbB-2蛋白表达水平呈显著相关(r=0.331,P=0.03)。结论结直肠癌中C-erbB-2基因启动子区CpG岛的低甲基化可能在C-erbB-2蛋白过度表达中起一定作用,有望成为有用的肿瘤分子诊断标记和治疗靶点。

The methylation status of CpG island in the promoter region of C-erbB-2 gene and the correlation of the methylation level of C-erbB-2 gene with the C-erbB-2 oncoprotein expression in colorectal carcinoma

Objective To explore the methylation status of CpG island in the promoter region of C-erbB-2 gene and the expression of C-erbB-2 oncoprotein in colorectal carcinoma tissues and realize their correlation.Methods The methylation patterns of CpG island in the promoter region of the C-erbB-2 gene in 43 pathologically confirmed carcinoma tissues and the matched adjacent tissues were detected by the methylation specific polymerase chain reaction(MSP).The C-erbB-2 oncoprotein was examined by immunohistochemistry(IHC).Results The methylation rate of CpG island in the promoter region of the C-erbB-2 in tumor tissues was significantly lower than that in matched adjacent tissues(44.2% vs 74.4%,P=0.004).The percentage of C-erbB-2 oncoprotein overexpression was significantly higher in carcinoma tissues than that in matched adjacent tissues(67.4% vs 27.9%,P=0.000).The C-erbB-2 oncoprotein overexpression was significantly associated with clinical stage.The hypomethylation of CpG island in the promoter region of the C-erbB-2 in carcinoma tissues was correlated with C-erbB-2 oncoprotein overexpression(r=0.331,P=0.03).Conclusions The hypomethylation of CpG island in the promoter region of C-erbB-2 gene would play a certain role in C-erbB-2 oncoprotein overexpression in colorectal carcinoma and it would be a valuable marker as cancer molecular diagnosis and a therapy target.