胃癌组织中MGMT、RASSF1A基因启动子区甲基化研究

The Expression and Promoter Hypermethylation Status of MGMT, RASSF1A in Gastric Cancer

摘要: 目的：探讨MGMT、RASSF1A启动子甲基化状况在胃癌发生、发展中的作用。方法：用甲基特异性聚合酶扩增链式反应(methylation specific PCR, MSP)检测60例胃癌组织及相应癌旁正常组织MGMT、RASSF1A基因启动子的甲基化状况，用实时荧光定量逆转录–多聚合酶链反应(real-time RT-PCR)和免疫组织化学SP法分别检测基因MGMT、RASSF1A的mRNA和蛋白的表达情况。结果：胃癌组织中MGMT、RASSF1A基因的甲基化阳性率较正常组织明显升高(P < 0.05)。胃癌组织中MGMT和RASSF1AmRNA阳性表达率明显低于正常组织(P < 0.05)。胃癌组织MGMT、RASSF1A蛋白表达明显低于正常组织。结论：胃癌组织中存在一定程度的MGMT、RASSF1A基因启动子高甲基化和蛋白表达缺失,是胃癌发生的重要途径之一。

Abstract: Objective: To investigate the functions of hypermethylation of MGMT and RASSF1A genes in human gastric cancer. Methods: Methylation status of the MGMT and RASSF1Agenes in 60 gastric carcinoma tissues and 60 paired surgical marginal normal gastric tissues were detected using methylation-specific PCR. Real-time RT-PCR was used to detect the expression of MGMT and RASSF1A, and immunohistochemistry was used to detect the expression of MGMT and RASSF1Aproteins in the above samples. Results: The positive rates of promoter methylation of the MGMT and RASSF1Agenes were significantly higher in gastric cancer than those in normal tissue (both P < 0.05). The positive rates of MGMT and RASSF1AmRNA expression in gastric cancer were significantly lower than those in normal tissues (both P < 0.05). The expression of MGMT and RASSF1A proteins were significantly higher in gastric cancer than those in normal tissue. Conclusion: Hypermethylation of CpG island and loss of the expression in MGMT and RASSF1A genes were existed in gastric cancer, and it possibly plays a key role in carcinogenesis of gastric cancer.