胶质母细胞瘤MGMT基因启动子甲基化、MGMT蛋白表达和预后相关性分析

目的探讨脑胶质母细胞瘤中O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化状态和MGMT蛋白表达水平与临床预后的相关性。方法收集119例人脑胶质母细胞瘤石蜡包埋样本,提取基因组DNA并进行亚硫酸氢盐修饰,用MethyLight法检测MGMT基因启动子甲基化状态,用免疫组织化学染色法检测MGMT蛋白表达水平,对MGMT基因启动子甲基化状态和MGMT表达水平与患者预后行相关性分析。结果在119例胶质母细胞瘤样本中,有42例检测到MGMT基因启动子甲基化,甲基化发生率为35.3%(42/119例),MGMT基因启动子甲基化与无进展生存期(P=0.011)及总体生存期(P=0.036)延长相关。MGMT蛋白表达水平和临床预后无相关性(P0.05),与MGMT基因启动子甲基化状态之间也无相关性(P0.05)。结论 MGMT基因启动子甲基化与胶质母细胞瘤患者预后呈正相关,由免疫组化法测得的MGMT蛋白表达水平和预后及基因启动子甲基化之间无关联性,MGMT基因启动子甲基化状态可以作为评判预后的生物学指标之一。

The Correlation between Aberrant Promoter Methylation of MGMT and Immunohistochemical Expression with Clinical Prognosis in Glioblastoma Multiforme

Aim To explore the correlation between the methylation status of MGMT promoter and MGMT protein expression levels in GBM and patients' survival,determine the methylation status of the MGMT promoter and the MGMT protein expression in gliomas,and analyze the correlation between MGMT methylation status and patients' outcome.Methods 119 formalin-fixed and paraffin-embedded GBM tissue samples were obtained after informed consent from adult patients.Genomic DNA was extracted and MGMT methylation status was measured with MethyLight assay after bisulfite treatment.The protein expression levels of MGMT were determined by immunohistochemical staining.The correlation between MGMT methylation status and MGMT expression levels was measured with Chi-square test,and the correlation between patients' outcome and MGMT methylation status or MGMT expression levels was determined by log-rank tests.Results The MGMT promoter was found to be methylated in 35.3％ patients (42/119).A significant correlation was observed between MGMT promoter methylation and patients' survival (PFS,P=0.011 and OS,P=0.036).No correlation was found between MGMTpromoter methylation and MGMT expression determined by immunohistochemical staining (P＞0.05),nor MGMT expression and patients' survival (P＞0.05).Conclusion The results supported that MGMT promoter methylation status may be more suitable as a predictive biomarker than the MGMT expression in the treatment of patients with GBM.