胶质瘤MGMT启动子甲基化及其临床意义

摘要

目的 分析O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化状态及其与胶质瘤临床病理特征、预后的关系.方法 收集2012年1月至2013年6月间行手术治疗的70例胶质瘤组织和14例非肿瘤患者正常脑组织,采用甲基化特异性PCR法(MSP)检测MGMT甲基化水平,分析其与胶质瘤临床病理特征的关系.比较不同MGMT甲基化状态的高、低级别胶质瘤患者的总生存(OS),Cox比例风险回归模型分析影响低级别胶质瘤患者的OS的因素.结果 70例胶质瘤患者中48例(68. 6％)MGMT基因启动子甲基化,而正常脑组织标本中仅2例(14. 3％)MGMT甲基化,差异有统计学意义(P＜0. 05).MGMT甲基化与年龄、性别、肿瘤类型、KPS评分、p53和Ki-67表达无关(P＞0. 05);与病理分级有关(P＜0. 05).低级别脑胶质瘤患者中,MGMT甲基化患者中位OS为30个月,明显长于非甲基化者的11个月,差异具有统计学意义(P＜0. 05).单因素分析显示WHO病理分级、烷化剂化疗、MGMT甲基化与低级别脑胶质瘤患者OS有关(P＜0. 05).多因素分析WHOⅡ级、未接受烷化剂化疗、MGMT非甲基化是影响低级别胶质瘤患者OS的独立危险因素(P＜0. 05).结论 MGMT甲基化与胶质瘤的发生、发展有关,在判断胶质瘤恶性度、评估预后及指导临床治疗方面具有一定的价值.%Objective To analyze the methylation status of promoter of O6-methylguanine-DNA methyltransferase (MGMT) gene and its relationship with clinicopathological features and prognosis of glioma. Methods The methylation level of MGMT was detected by methylation specific polymerase chain reaction (MSP) in 70 glioma tissues and 14 normal brain tissues of non-tumor patients who underwent surgical treatment from January 2012 to June 2013. The relationship between MGMT methylation and clinicopathological features was analyzed. Overalll survival (OS) of patients with high and low grade glioma with different MGMT methylation status was compared. Cox proportional regression model was used to analyze the factors affecting OS in low-grade glioma patients. Results Of 70 glioma patients, 48 (68. 6％) had MGMT promoter methylation, while only 2 (14. 3％) had MGMT methylation in normal brain tissues (P＜0. 05). MGMT methylation was not correlated with age, sex, tumor type, KPS score, p53 and Ki-67 expression (P＞0. 05), but with pathological grade (P＜0. 05). The median OS of MGMT methylated glioma patients was 30 months, significantly longer than that of non-methylated glioma patients for 11 months (P＜0. 05). Univariate analysis showed that WHO pathological grade, alkylating agent chemotherapy and MGMT methylation were associated with OS in low-grade glioma patients (P ＜ 0. 05). Multivariate analysis showed that WHO grade Ⅱ, non-alkylation chemotherapy and MGMT non-methylation were independent risk factors for OS in lowgrade glioma patients (P＜0. 05). Conclusion MGMT methylation is related to the occurrence and development of glioma. It has certain value in judging the malignancy of glioma, evaluating prognosis and guiding clinical treatment.