The prognostic value of MGMT promoter methylation in Glioblastoma multiforme: a meta-analysis

The prognostic significance of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation on Glioblastoma multiforme (GBM) remains controversial. A meta-analysis of published studies investigating the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients was performed. A total of 2,986 patients from 30 studies were included in the meta-analysis. In all, the frequency of MGMT promoter methylation was 44.27 %. Five studies undertook univariate analyses and nine undertook multivariate analyses of MGMT promoter methylation on PFS. The pooled hazard ratio (HR) estimate for PFS was 0.72 (95 % CI 0.55-0.95) by univariate analysis and 0.51 (95 % CI 0.38-0.69) by multivariate analysis. The effect of MGMT promoter methylation on OS was evaluated in 15 studies by univariate analysis and 14 studies by multivariate analysis. The combined HR was 0.67 (95 % CI 0.58-0.78) and 0.49 (95 % CI 0.38-0.64), respectively. For GBM patients treated with Alkylating agent, the meta-risk remained highly significant by both univariate (HR = 0.58; 95 % CI 0.42-0.79) and multivariate analysis (HR = 0.42; 95 % CI 0.29-0.60). This study showed that MGMT promoter methylation was associated with better PFS and OS in patients with GBM regardless of therapeutic intervention, and associated with longer OS in GBM patients treated with alkylating agents.