Prognostic impact and predictive value of MGMT promoter methylation in different molecular subtypes of diffuse glioma
Zhang Jing
Liu Yanwei
Abstract：Objective To explore the prognostic impact and predictive value of O6-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 prospective clinical trials.
Keywords：gliomaO6-methylguanine-DNA methyltransferasepromoter methylationprognostic factors
Publication Date：2025-01-19
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 24-30 )