非小细胞肺癌中MGMT基因启动子过甲基化状况及k-ras表达的相关性

Promoter Hypermethylation of MGMT Gene and Expression of K-ras in Human Non-small-cell Lung Cancer

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 relationgship between the promoter hypermethylation of O6-methylguanine DNA methyltransferase （MGMT） gene and expression of K-ras in non-small-cell lung cancer（NSCLC）.Methods Methylation specific PCR （MSP） and immunohistochemical methods were used to detected methylation status of MGMT gene and K-ras expression in 98 patients with NSCLC.Results The rate of the promoter hypermethylation of MGMT gene in 98 NSCLC was 31.6%（31/98）,the rate of expression of K-ras was 46.9%（46/98）.The MGMT gene promoter methylation rate and K-ras protein expression rate in the control group of 10 normal lung tissue both was 0（0/98）.The promoter hypermethylation rate of MGMT gene and the expression of K-ras in NSCLC patients with the stage Ⅲ of P-TNM,lymph node metastasis and smoking patients,was higher than that in patients with stage Ⅰ～Ⅱ,no lymph node metastasis and without smoking.（all P0.05）.There was positive correlation between the promoter hypermethylation of MGMT and the expression of K-ras in NSCLC（Rs=0.591,P0.05）.Conclusion The promoter hypermethylation of MGMT gene may lead to the activation of K-ras gene.They may take part in NSCLC evolvement.