The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a m
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RESEARCH ARTICLE
Open Access
The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis Huy Gia Vuong1,2, Thu Quynh Nguyen3, Tam N. M. Ngo3, Hoang Cong Nguyen3, Kar-Ming Fung1,2 and Ian F. Dunn4*
Abstract Background: There are controversial results concerning the prognostic implication of TERT promoter mutation in glioma patients concerning MGMT status. In this meta-analysis, we investigated whether there are any interactions of these two genetic markers on the overall survival (OS) of glioma patients. Methods: Electronic databases including PubMed and Web of Science were searched for relevant studies. Hazard ratio (HR) and its 95% confidence interval (CI) for OS adjusted for selected covariates were calculated from the individual patient data (IPD), Kaplan-Meier curve (KMC), or directly obtained from the included studies. Results: A total of nine studies comprising 2819 glioma patients were included for meta-analysis. Our results showed that TERT promoter mutation was associated with a superior outcome in MGMT-methylated gliomas (HR = 0.73; 95% CI = 0.55–0.98; p-value = 0.04), whereas this mutation was associated with poorer survival in gliomas without MGMT methylation (HR = 1.86; 95% CI = 1.54–2.26; p-value < 0.001). TERT-mutated glioblastoma (GBM) patients with MGMT methylation benefited from temozolomide (TMZ) treatment (HR = 0.33; 95% CI = 0.23–0.47; pvalue < 0.001). MGMT methylation was not related with any improvement in OS in TERT-wild type GBMs (HR = 0.80; 95% CI = 0.56–1.15; p-value = 0.23). Conclusions: The prognostic value of TERT promoter mutation may be modulated by MGMT methylation status. Not all MGMT-methylated GBM patients may benefit from TMZ; it is possible that only TERT-mutated GBM with MGMT methylation, in particular, may respond. Keywords: Glioma, Glioblastoma, TERT, MGMT, Temozolomide, Overall survival, Meta-analysis
* Correspondence: [email protected] 4 Department of Neurosurgery, Oklahoma University Health Sciences Center, Oklahoma City, OK 73104, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain
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