Predictive value of MGMT promoter methylation on the survival of TMZ treated IDH-mutant glioblastoma  

作　　者：Ruichao Chai Guanzhang Li Yuqing Liu Kenan Zhang Zheng Zhao Fan Wu Yuzhou Chang Bo Pang Jingjun Li Yangfang Li Tao Jiang Yongzhi Wang 

机构地区：[1]Department of Molecular Neuropathology,Beijing Neurosurgical Institute,Chinese Glioma Genome Atlas Network(CGGA),Capital Medical University,Beijing 100070,China [2]Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China

出　　处：《Cancer Biology & Medicine》2021年第1期271-282,共12页癌症生物学与医学（英文版）

基　　金：funded by the National Natural Science Foundation of China(Grant Nos.81903078 and 81773208);the Beijing Nova Program(Grant No.Z201100006820118);the National Key Research and Development Program of China(Grant No.2018YFC0115604);the National Natural Science Foundation of China(NSFC)/Research Grants Council(RGC)Joint Research Scheme(Grant No.81761168038);the Beijing Municipal Administration of Hospitals’Mission Plan(Grant No.SML20180501);the CAMS Innovation Fund for Medical Sciences(Grant No.2019-I2M-5-021);the Public Welfare Development and Reform Pilot Project of the Beijing Medical Research Institute(Grant No.JYY 2019-5)。

摘　　要：Objective:O6 methylguanine-DNA methyltransferase(MGMT)promoter methylation is a biomarker widely used to predict the sensitivity of IDH-wildtype glioblastoma to temozolomide therapy.Given that the IDH status has critical effects on the survival and epigenetic features of glioblastoma,we aimed to assess the role of MGMT promoter methylation in IDH-mutant glioblastoma.Methods:This study included 187 IDH-mutant glioblastomas and used 173 IDH-wildtype glioblastomas for comparison.KaplanMeier curves and multivariate Cox regression were used to study the predictive effects.Results:Compared with IDH-wildtype glioblastomas,IDH-mutant glioblastomas showed significantly higher(P<0.0001)MGMT promoter methylation.We demonstrated that MGMT promoter methylation status,as determined by a high cutoff value(≥30%)in pyrosequencing,could be used to significantly stratify the survival of 50 IDH-mutant glioblastomas receiving temozolomide therapy(cohort A);this result was validated in another cohort of 25 IDH-mutant glioblastomas(cohort B).The median progression-free survival and median overall survival in cohort A were 9.33 and 13.76 months for unmethylated cases,and 18.37 and 41.61 months for methylated cases,and in cohort B were 6.97 and 9.10 months for unmethylated cases,and 23.40 and 26.40 months for methylated cases.In addition,we confirmed that the MGMT promoter methylation was significantly(P=0.0001)correlated with longer OS in IDH-mutant patients with GBM,independently of age,gender distribution,tumor type(primary or recurrent/secondary),and the extent of resection.Conclusions:MGMT promoter methylation has predictive value in IDH-mutant glioblastoma,but its cutoff value should be higher than that for IDH-wildtype glioblastoma.

关 键 词：GLIOBLASTOMA O6methylguanine-DNA methyltransferase isocitrate dehydrogenase TEMOZOLOMIDE PYROSEQUENCING 

分 类 号：R739.41[医药卫生—肿瘤]