The interaction between TERT promoter mutation and MGMT promoter methylation on overall survival of glioma patients: a meta-analysis

BMC Cancer

Ian F. Dunn¹  Huy Gia Vuong²  Kar-Ming Fung²  Thu Quynh Nguyen³  Hoang Cong Nguyen³  Tam N. M. Ngo³ 

[1] Department of Neurosurgery, Oklahoma University Health Sciences Center, 73104, Oklahoma City, OK, USA;Department of Pathology, Oklahoma University Health Sciences Center, 73104, Oklahoma City, OK, USA;Stephenson Cancer Center, Oklahoma University Health Sciences Center, 73104, Oklahoma City, OK, USA;Faculty of Medicine, Pham Ngoc Thach University of Medicine, 700-000, Ho Chi Minh City, Vietnam;

关键词: Glioma;    Glioblastoma;    TERT;    MGMT;    Temozolomide;    Overall survival;    Meta-analysis;   

DOI  :  10.1186/s12885-020-07364-5

来源: Springer

【 摘 要 】

BackgroundThere 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.MethodsElectronic 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.ResultsA 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; p-value < 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).ConclusionsThe 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.

【 授权许可】

CC BY