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J Cell Physiol. 2018 Jan;233(1):378-386. doi: 10.1002/jcp.25896. Epub 2017 May 16.

The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials.

Author information

1
Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2
Department of Modern Sciences and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
3
Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
4
Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
5
Department of Pediatric Surgery, School of Medicine, Mashhad University of Medical Sciences, Sarvar Children's Hospital, Endoscopic and Minimally Invasive Surgery Research Center, Mashhad, Iran.

Abstract

The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) is suggested to be associated with resistance to alkylating agents such as Temozolomide which is being used in treatment of patients with glioblastoma (GBM). Therefore, we evaluated the associations between MGMT promoter methylation and prognosis of patients with glioblastoma (GBM). Data were extracted from publications in Embase, PubMed, and the Cochrane Library. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained and 4,097 subjects were enrolled. Data from 34 studies showed that MGMT methylated patients had better OS, compared to GBM unmethylated patients (pooled HRs, 0.494; 95%CI 0.412-0.591; p = 0.001). Meta-analysis of 10 eligible studies reporting on PFS, demonstrated that MGMT promoter methylation was not significantly associated with better PFS (pooled HRs, 0.653; 95%CI 0.414-1.030; p = 0.067). GBM patients with MGMT methylation were associated with longer overall survival, although this effect was not detected for PFS. Moreover, we performed further analysis in patients underwent a comprehensive imaging evaluation. This data showed a significant association with better OS and PFS, although further studies are warranted to assess the value of emerging marker in prospective setting in patients with glioblastoma as a risk stratification biomarker in clinical management of the patients.

KEYWORDS:

MGMT methylation; glioblastoma; overall survival; progression-free survival

PMID:
28266716
DOI:
10.1002/jcp.25896
[Indexed for MEDLINE]

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