MGMT启动子甲基化对不同分子亚型弥漫性胶质瘤的预后影响与预测价值  

Prognostic impact and predictive value of MGMT promoter methylation in different molecular subtypes of diffuse glioma

作　　者：张静[1] 刘彦伟[1] Zhang Jing;Liu Yanwei(Department of Radiotherapy,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京天坛医院放疗科,北京100070

出　　处：《中国微侵袭神经外科杂志》2025年第1期24-30,共7页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：国家重点研发计划常见多发病防治研究专项(编号:2023YFC2510005)。

摘　　要：目的基于中国脑胶质瘤基因组(The Chinese Glioma Genome Atlas,CGGA)数据库,探索O^(6)-甲基鸟嘌呤-DNA甲基转移酶(O^(6)-methylguanine-DNA methyltransferase,MGMT)启动子甲基化对弥漫性胶质瘤不同分子亚型的预后影响与预测价值。方法筛选3438例弥漫性胶质瘤患者的临床资料和分子病理信息,排除既往胶质瘤病史和原发胶质母细胞瘤病例,共771例可明确分子分型的WHO 2~3级胶质瘤和分子定义的WHO 4级星形细胞瘤患者纳入研究,中位随访68.6个月。临床病理特征比较采用t检验或卡方检验,Kaplan-Meier统计总生存期(overall survival,OS)和无进展生存期(progression free survival,PFS),Cox回归用于研究不同因素对OS和PFS的影响。结果771例弥漫性胶质瘤包括270例异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)突变及1p/19q共缺失少突胶质细胞瘤(WHO 2级:163例,3级:107例),367例IDH突变型星形细胞瘤(2级:210例,3级:107例,4级:50例)和134例IDH野生型星形细胞瘤。MGMT启动子甲基化在IDH突变及1p/19q共缺失少突胶质细胞瘤、IDH突变型星形细胞瘤和IDH野生型星形细胞瘤的发生率分别为74.8%、60.9%和35.1%。WHO 2级IDH突变型星形细胞瘤中MGMT启动子甲基化患者能从术后化疗中获益(HR=3.047,95%CI:1.125~8.254,P=0.028),多因素Cox回归分析显示:MGMT启动子甲基化是IDH突变型星形细胞瘤的独立预后因素(HR=2.083,95%CI:1.127~3.848,P=0.001),与少突胶质细胞瘤、IDH野生型星形细胞瘤患者预后无显著相关性。结论弥漫性胶质瘤MGMT启动子甲基化对不同分子分型的预后影响和预测价值不同,本研究为临床治疗和开展前瞻性临床试验提供参考。Objective To explore the prognostic impact and predictive value of O^(6)-methylguanine-DNA methyltransferase(MGMT)promoter methylation in different molecular subtypes of diffuse gliomas based on a large sample of The Chinese Glioma Genome Atlas(CGGA)database.Methods Clinical data and molecular pathology information of 3438 diffuse glioma patients were screened,previous history of glioma and primary glioblastoma cases were excluded,and a total of 771 patients with definable molecular staging of WHO grade 2-3 gliomas and molecularly-defined WHO grade 4 astrocytomas were included in the study with a median follow-up of 68.6 months.Clinicopathologic characteristics were compared using t-test or chi-square test,Kaplan-Meier statistics for overall survival(OS)and progression-free survival(PFS),and Cox regression was used to investigate the effects of different factors on OS and PFS.Results The 771 diffuse gliomas included 270 cases of oligodendrogliomas with isocitrate dehydrogenase(IDH)mutation and 1p/19q co-deletion(WHO grade 2:163 cases,grade 3:107 cases),367 cases of IDH-mutant astrocytomas(grade 2:210 cases,grade 3:107 cases,grade 4:50 cases)and 134 cases of IDH wild-type astrocytomas.The prevalence of MGMT promoter methylation in IDH mutant and 1p/19q co-deletion oligodendrogliomas,IDH mutant astrocytomas,and IDH wild-type astrocytomas was 74.8%,60.9%,and 35.1%respectively.MGMT promoter methylation in WHO grade 2 IDH mutant astrocytoma patients could benefit from postoperative chemotherapy(HR=3.047,95%CI:1.125-8.254,P=0.028).Multifactorial Cox regression analysis showed that MGMT promoter methylation was an independent prognostic factor for IDH mutant astrocytomas(HR=2.083,95%CI:1.127-3.848,P=0.001),but had no significant correlation with the prognosis of oligodendrogliomas or IDH wild-type astrocytomas.Conclusions The prognostic impact and predictive value of MGMT promoter methylation in diffuse gliomas vary across molecular typing,and this study provides a reference for clinical treatment and conducting prospec

关 键 词：神经胶质瘤 O^(6)-甲基鸟嘌呤-DNA甲基转移酶 启动子甲基化 预后因素 

分 类 号：R739.41[医药卫生—肿瘤] R730.264[医药卫生—临床医学]