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目的探讨非小细胞肺癌(NSCLC)中DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)的过甲基化状况、K-ras的表达及其相关性。方法采用甲基化特异性PCR(MSP)及免疫组化的方法 ,检测术后98例NSCLC组织MGMT基因过甲基化状况、K-ras的表达。结果 98例NSCLC组织中MGMT基因启动子甲基化率为31.6%(31/98),K-ras的阳性表达率为46.9%(46/98),对照组10例正常肺组织中MGMT基因启动子甲基化率及K-ras蛋白的阳性表达率均为0(0/98)。在伴有吸烟史、淋巴结转移、P-TNM分期Ⅲ期的NSCLC患者中,MGMT基因过甲基化率及K-ras的阳性表达率均高于不伴有吸烟史、淋巴结转移及Ⅰ～Ⅱ期的患者(P均<0.05),MGMT基因过甲基化率与K-ras的阳性表达率呈正相关(Rs=0.591,P(0.05)。结论在NSCLC中,MGMT基因启动子过甲基化导致K-ras基因的激活,共同参与非小细胞肺癌的发生、发展。
Objective To investigate the hypermethylation and K-ras expression of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in non-small cell lung cancer (NSCLC). Methods The methylation-specific PCR (MSP) and immunohistochemistry were used to detect the hypermethylation status and K-ras expression of MGMT gene in 98 NSCLC patients. Results The promoter methylation rate of MGMT gene was 31.6% (31/98) in 98 cases of NSCLC tissues and 46.9% (46/98) in K-ras. The MGMT gene promoter in 10 normal lung tissues of control group The methylation rate and the K-ras protein positive rate were all 0 (0/98). In NSCLC patients with smoking history, lymph node metastasis and P-TNM stage Ⅲ, the over-methylation rate of MGMT gene and the positive rate of K-ras expression were higher than those without smoking history, lymph node metastasis and Ⅰ ~ Ⅱ (P <0.05), the methylation rate of MGMT gene was positively correlated with the positive expression rate of K-ras (Rs = 0.591, P <0.05) .Conclusions In NSCLC, MGMT gene promoter hypermethylation Leading to the activation of K-ras gene and participating in the occurrence and development of non-small cell lung cancer.