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Is the prognostic significance of O6-methylguanine-DNA methyltransferase promoter methylation equally important in glioblastomas of patients from different continents? A systematic review with meta-analysis

Authors Meng W, Jiang Y, Ma J

Received 26 April 2017

Accepted for publication 14 July 2017

Published 20 September 2017 Volume 2017:9 Pages 411—425

DOI https://doi.org/10.2147/CMAR.S140447

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Alexandra R. Fernandes


Wei Meng,1,* Yangyang Jiang,2,* Jie Ma1

1Department of Pediatric Neurosurgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of Neurosurgery, Shanghai Deji Hospital, Shanghai Neuromedical Center Affiliated to Qingdao University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Background: O6-methylguanine-DNA methyltransferase (MGMT) is an independent predictor of therapeutic response and potential prognosis in patients with glioblastoma multiforme (GBM). However, its significance of clinical prognosis in different continents still needs to be explored.
Patients and methods: To explore the effects of MGMT promoter methylation on both progression-free survival (PFS) and overall survival (OS) among GBM patients from different continents, a systematic review of published studies was conducted.
Results: A total of 5103 patients from 53 studies were involved in the systematic review and the total percentage of MGMT promoter methylation was 45.53%. Of these studies, 16 studies performed univariate analyses and 17 performed multivariate analyses of MGMT promoter methylation on PFS. The pooled hazard ratio (HR) estimated for PFS was 0.55 (95% CI 0.50, 0.60) by univariate analysis and 0.43 (95% CI 0.38, 0.48) by multivariate analysis. The effect of MGMT promoter methylation on OS was explored in 30 studies by univariate analysis and in 30 studies by multivariate analysis. The combined HR was 0.48 (95% CI 0.44, 0.52) and 0.42 (95% CI 0.38, 0.45), respectively.
Conclusion: In each subgroup divided by areas, the prognostic significance still remained highly significant. The proportion of methylation in each group was in inverse proportion to the corresponding HR in the univariate and multivariate analyses of PFS. However, from the perspective of OS, compared with data from Europe and the US, higher methylation rates in Asia did not bring better returns.

Keywords: O6-methylguanine-DNA methyltransferase, methylation, glioblastoma, prognosis, meta-analysis

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