title: The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials.
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.
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam Moradi
authors.initials: MM
authors.lastname: Binabaj
authors.affiliation: Department of Modern Sciences and Technology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Afsane
authors.initials: A
authors.lastname: Bahrami
authors.affiliation: Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: ShahidSales
authors.affiliation: 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.
authors.forename: Marjan
authors.initials: M
authors.lastname: Joodi
authors.affiliation: Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Joudi Mashhad
authors.affiliation: Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mahdi
authors.identifier: http://orcid.org/0000-0002-5247-4043
authors.initials: SM
authors.lastname: Hassanian
authors.affiliation: Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Kazem
authors.initials: K
authors.lastname: Anvari
authors.affiliation: Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.|Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.identifier: http://orcid.org/0000-0002-4968-0962
authors.initials: A
authors.lastname: Avan
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: MGMT methylation; glioblastoma; overall survival; progression-free survival