胃癌组织中MGMT基因甲基化与DNMT1蛋白表达的关系

Relationship between Methylation of MGMT Gene and Protein Expression of DNMT1 in Gastric Cancer

背景:研究表明MGMT基因启动子区甲基化与包括胃癌在内的多种恶性肿瘤密切相关。DNA甲基转移酶1(DNMT1)在多种肿瘤组织中的表达上调。但目前关于胃癌组织中MGMT基因甲基化状态与DNMT1表达关系的研究少见。目的:探讨MGMT基因甲基化、DNMT1蛋白表达与胃癌的关系。方法:采用甲基化特异性PCR(MSP)技术检测60例胃腺癌组织及其相应癌旁组织中MGMT基因启动子区甲基化状态,RT-PCR、免疫组化法分别检测MGMT、DNMT1 mRNA和蛋白表达。结果:胃癌组织中MGMT基因启动子区甲基化率明显高于癌旁组织(45.0%对13.3%,P<0.001)。胃癌组织中MGMT mRNA阳性表达率显著低于癌旁组织(41.7%对93.3%,P<0.001),而DNMT1 mRNA阳性率明显升高(76.7%对18.3%,P<0.001)。MGMT mRNA阴性表达的胃癌组织中其基因启动子甲基化率较阳性表达者升高(57.1%对28.0%,P<0.05)。胃癌组织中MGMT蛋白表达与DNMT1蛋白表达呈负相关(r=-0.795,P<0.01)。结论:MGMT基因启动子区高甲基化和DNMT1高表达可能与胃癌的发生、发展有关。DNMT1可能调控MGMT基因的甲基化过程。

Studies have shown that promoter methylation of MGMT gene is closely related to many malignant tumor including gastric cancer. DNA methyltransferase 1 （DNMT1） is highly expressed in many malignant tumor tissues. However, studies on relationship between methylation of MGMT gene and DNMT1 expression in gastric cancer are rare. Aims： To investigate the relationship between methylation of MGMT gene, protein expression of DNMT1 and gastric cancer. Methods： Promoter methylation status of MGMT gene in 60 gastric adenocarcinoma tissues and corresponding paracancerous tissues were detected by methylation-specific PCR （MSP）. RT-PCR and immunohistochemistry were used to measure mRNA and protein expressions of MGMT and DNMT1, respectively. Results： Methylation rate of MGMT gene promoter in gastric cancer was significantly higher than that in paracancerous tissue （45.0% vs. 13.3%, P 〈 0. 001 ）. The positivity rate of MGMT mRNA in gastric cancer was significantly lower than that in paracancerous tissue （41.7% vs. 93.3%, P 〈 0. 001 ）, while the positivity rate of DNMTI mRNA expression in gastric cancer was significantly higher than that in paracancerous tissue （76.7% vs. 18.3% , P 〈 0. 001 ）. Methylation rate of MGMT promoter in MGMT mRNA- negative expressed gastric cancer tissue was significantly higher than that in MGMT mRNA-positive expressed gastric cancer tissue （57.1% vs. 28.0% , P 〈0.05）. It showed a negative correlation between MGMT protein expression and DNMT1 protein expression in gastric cancer tissue （r = -0.795, P 〈 0.01 ）. Conclusions： Promoter methylation of MGMT gene and high expression of DNMT1 may be associated with the development and progression of gastric cancer.