胃癌组织中miR-148a基因甲基化状态与DNA甲基转移酶1的关系

Association between the methylation status of miR-148a gene and DNA methyltransferase 1 in gastric cancer tissues

目的探讨胃癌组织中miR-148a基因甲基化与临床病理特征、DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)表达的关系。方法 40例胃癌患者的胃癌组织(胃癌组)及其癌旁组织(癌旁组),采用荧光定量PCR法检测2组miR-148a表达情况,采用甲基化特异性PCR检测miR-148a甲基化状态,采用免疫组织化学法检测DNMT1表达情况。结果胃癌组miR-148a表达水平明显低于癌旁组(P<0.01),胃癌组miR-148a甲基化率为70.0%,癌旁组为17.5%,2组比较差异有统计学意义(P<0.05),胃癌组miR-148a甲基化状态在肿瘤大小、浸润深度上差异有统计学意义(P<0.05);胃癌组DNMT1蛋白阳性率为72.5%,癌旁组为27.5%,2组比较差异有统计学意义(P<0.05),胃癌组DNMT1阳性率与miR-148a甲基化状态呈正相关(r=0.33,P<0.05)。结论胃癌组织中miR-148a基因呈高度甲基化状态,可能与DNMT1过表达有关。

Objective To detect the methylation status of miR-148a gene in gastric cancer tissues, and investigate its association with clinicopathologic features and the expression of DNA methyltransferase 1 （DNMT1）. Methods The expression of miR-148a was detected in 40 case of gastric cancer and their matched non-tumor adjacent tissue specimens by using fluorescence quantitative PCR technique. Methylation-specific PCR technique was used to examine the methylation status of miR- 148a and the expression of DNMT1 was analyzed with immunohistoehemical staining. Results The expression of miR-148a was significantly lower in gastric cancer than that in the adjacent tissue （P 〈 0.01）. The methylation rate of miR-148a was 70.0% and 17.5% in gastric cancer and the adjacent tissue specimens respectively （P〈 0.05）. The methylation status differed significantly in tumor size and invasive depth （P〈0.05）. The positive rate of DNMT1 was 72.5% and 27.5% in gastric cancer and the adjacent tissue （P〈0.05）. The positive rate of DNMT1 was positively correlated with the methylation status of miR-148a in gastric cancer （r=0. 33, P 〈0.05）. Conclusion Hypermethylation of miR-148a is present in gastric cancer, and it may be related with the over-expression of DNMT1.