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Mol Neurobiol. 2014 Jun 10. [Epub ahead of print]

Correlation of Promoter Methylation in the MGMT Gene with Glioma Risk and Prognosis: a Meta-Analysis.

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  • 1Department of Neurology, First Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China.


Epigenetic silencing of the O 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been associated with decreased risk and longer survival in patients with glioma who receive alkylating agent. To derive a more precise estimate of this postulated relationship, a meta-analysis was performed based on existing relevant studies. By searching the Cochrane Library Database, CINAHL, Chinese Biomedical Database (CBM), EMBASE, PubMed, and Web of Science, we tabulated and analyzed parameters from each study, including susceptibility to glioma, disease-free survival (DFS), overall survival (OS), and clinical information on patients. Results were summarized through meta-analyses conducted using STATA software (version 12.0, Stata Corporation, and College Station, Texas USA). Hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were also calculated in this analysis. We combined individual patient data from eight cohort studies, which met our inclusion criteria, and examined a total of 573 patients with glioma. Our meta-analysis results demonstrated that MGMT methylation correlated with longer DFS and OS in glioma patients (DFS, HR = 1.62, 95 % CI = 0.67 ~ 2.56, P = 0.001; OS, HR = 1.74, 95 % CI = 1.16 ~ 2.33, P < 0.001, respectively). Ethnicity-stratified analyses revealed associations between aberrant methylation of MGMT and DFS in both Asian and Caucasian glioma patients (Asians, HR = 1.40, 95 % CI = 0.03 ~ 2.78, P = 0.046; Caucasians, HR = 1.89, 95 % CI = 0.28 ~ 3.50, P = 0.021, respectively), while similar associations were not found between aberrant MGMT methylation and OS in glioma patients (P > 0.05). This meta-analysis highlights the strong relations between aberrant MGMT methylation and longer DFS and OS in glioma patients. Thus, aberrant MGMT methylation may be a promising biomarker for prognosis of glioma.

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