非小细胞肺癌患者血清O6-甲基鸟嘌呤-DNA-甲基转移酶基因异常甲基化检测及其临床意义

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者血清中O6-甲基鸟嘌呤-DNA-甲基转移酶(O6-methylguanine-DNA-methyhransferase,MGMT)基因启动子区域甲基化的改变状况及其临床意义.方法 基因测序法检测62例NSCLC患者、30例肺部良性疾病患者和16例健康体检者血清中MGMT基因启动子区域甲基化状况,并分析其与临床特征的关系.结果 NSCLC患者血清MGMT基因甲基化检出率为27.42%(17/62),而肺部良性疾病患者和健康体检者血清未检出MGMT基因甲基化(Fisher精确概率法,P＜0.01).MGMT基因甲基化检出率与NSCLC患者年龄、性别、病理类型、分化程度无明显相关,但在晚期患者中检出率较高(P＜0.05).MGMT基因甲基化患者吸烟指数(年·支)明显高于非甲基化患者(P＜0.01).结论 MGMT基因异常甲基化可能在NSCLC发生、发展中起重要作用,有望成为NSCLC辅助诊断的分子标记.

Significance of MGMT hypermethylation in serum DNA of non-small cell lung cancer patients

Objective To detect the promoter methylation status of O6-methylguanine-DNA-methyhransferase(MGMT) gene in the serum of non-small cell lung cancer(NSCLC) patients and to discuss its clinical significance.Methods Serum DNA was extracted from 62 patients with NSCLC,30 patients with benign pulmonary disease and 16 health subjects with medical check-up.The methylation status of MGMT gene was detected by bisulfite genomic sequence and the correlation of methylation profiles with clinical characteristics was analyzed.Results Aberrant promoter methylation of MGMT was detected in 17 of 62 (27.42%) NSCLC patients,but in none of patients with benign pulmonary disease and health subjects with medical check-up(Fisher exact test,P＜0.01).The promoter hypermethylation of MGMT correlated with late stage(P＜0.05),but not with age,gender,histopathology or differentiation in NSCLC patients,The smoking index in methylated patients was higher than that in unmethylated patients(P＜0.01).Conclusions The promoter hypermethylation of MGMT may play an important role in the tumorigenesis and progression,and it is hopeful to become a biomarker for auxiliary diagnosis in NSCLC.