Abstract
BackgroundThe prognostic value of the status of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation measured by pyrosequencing assay (PSQ) among glioblastoma (GBM) patients was examined in meta-analysis.MethodsEligible studies that reported the association between the status of MGMT promoter methylation by PSQ and prognostic value of GBM patients from three electronic databases, like PubMed, EMBASE, and Cochrane library were involved in meta-analysis. Using Stata 11.0, the summarized hazard ratios (HRs) for overall survival (OS) and the progression-free survival (PFS) with 95 % confidence interval (CI) were calculated.ResultsEleven studies were included to evaluate the relationship between the status of MGMT promoter methylation and GBM patients’ survival. Overall, regardless of the cut-off value of methylation status of MGMT promoter by PSQ, methylated-positive patients were evidently associated with an improved HRs for OS (HRs = 0.50, 95 % CI = 0.35–0.66). For summary, progression-free survival (PFS) from four studies, the prognostic effect was also found (HRs = 0.56, 95 % CI = 0.32–0.80).ConclusionMethylation positivity of MGMT promoter by PSQ was related to an increased survival in GBM patients. Thus, the status of MGMT promoter methylation by PSQ might be used to be a prognostic biomarker, and GBM patients might have a vested interest in clinical application of standardized PSQ.
Highlights
The prognostic value of the status of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation measured by pyrosequencing assay (PSQ) among glioblastoma (GBM) patients was examined in meta-analysis
Since a landmark study by Hegi [11] 11 years ago, numerous studies have confirmed that methylation status of MGMT promoter can serve as a predictive factor for the outcome of GBM patients aged less than 60 years, following alkylating agent chemotherapy [12, 13], or a prognostic factor in non-elderly GBM patients [14]
PSQ is a sequence-by-synthesis method that is the only method respectively analyzing methylation levels of each CpGs and providing quantitative information on the percentage of CpGs methylation [16]. To our knowledge, this is the first meta-analysis that has evaluated the role of MGMT promoter methylation in predicting the prognosis of GBM patients. In this meta-analysis, because of the prognostic value of methylation status of MGMT promoter by PSQ for survival of GBM patients unclear and no in consensus, we summarized relevant data to quantify the prognostic value of methylation status of MGMT promoter by PSQ, using standard meta-analysis techniques, regardless of impact factors, such as age of patients, therapy modality, etc
Summary
The prognostic value of the status of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation measured by pyrosequencing assay (PSQ) among glioblastoma (GBM) patients was examined in meta-analysis. It was found that MGMT promoter methylation is a predictive marker for benefit from alkylating agents only in high-grade glioma patients with IDH1 wildtype, but 1p/19q loss in highgrade glioma patients with IDH1 mutant [7]. In this meta-analysis, the predictive or prognostic role of MGMT promoter methylation among GBM was assessed. Varying quantitative and qualitative assays, such as MSP, methylation-sensitive high-resolution melting and PSQ, and bisulfite sequencing [15] have been used to examine the methylation status of CpGs island that mainly regulates MGMT protein expression at the epigenetic level, in MGMT promoter. PSQ is a sequence-by-synthesis method that is the only method respectively analyzing methylation levels of each CpGs and providing quantitative information on the percentage of CpGs methylation [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
