The TERT promoter mutation status and MGMT promoter methylation status, combined with dichotomized MRI‐derived and clinical features, predict adult primary glioblastoma survival

• Published in: Cancer medicine (Malden, MA) MA), 2018-08, Vol.7 (8), p.3704-3712
• Main Authors: Shu, Chang, Wang, Qiong, Yan, Xiaoling, Wang, Jinhuan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarkers, Tumor - genetics; Brain cancer; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Clinical Cancer Research; Correlation analysis; Disease Management; DNA Methylation; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; Female; Gangrene; Genetic Predisposition to Disease; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - genetics; Glioblastoma - mortality; Humans; Kaplan-Meier Estimate; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical prognosis; MGMT; Middle Aged; MRI; Mutation; Necrosis; Original Research; primary glioblastoma; Prognosis; Promoter Regions, Genetic; Proportional Hazards Models; Retrospective Studies; Survival; Survival analysis; Telomerase - genetics; Telomerase - metabolism; TERT; Tomography, X-Ray Computed; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Workflow
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1666

Purpose This study aimed to integrate the TERT promoter mutation status, MGMT promoter methylation status, MRI‐derived features, and clinical features into a survival analysis model to better understand adult primary glioblastoma prognosis‐related markers. Method A total of 304 adult glioblastoma samples collected after surgical resection were selected for retrospective analysis, and Sanger sequencing was performed to detect IDH and TERT promoter mutations. The methylation of the MGMT promoter was analyzed by pyrosequencing, and MRI‐derived and clinical features were dichotomized into easily acquired variables. Random survival forest analysis, Kaplan‐Meier analysis, Cox proportional hazard regression, and LASSO regression were performed for the survival analysis, and ROC analysis and Pearson's chi‐squared test were employed for the correlation analysis. Results Wild‐type IDH was present in 89.8% of the adult glioblastoma samples, and TERT promoter mutations and MGMT promoter methylation were observed in 66.42% and 38.49% of all adult primary glioblastomas, respectively. Age and MGMT promoter methylation were identified as independent prognostic biomarkers, and the TERT promoter mutation status and MGMT promoter methylation status, when combined with other tumor‐related factors, generated several different survival subgroups. None of the factors investigated in this study predicted the MGMT promoter status, and MRI‐detected necrosis was positively associated with TERT promoter mutations. Conclusion MGMT promoter methylation and TERT promoter mutations, combined with MRI‐derived and clinical features, revealed different survival subgroups with distinct responses to current treatments, and this information increases the ability to predict the survival of adult primary glioblastoma patients. MRI‐detected necrosis often indicates the presence of TERT promoter mutations. MGMT promoter methylation and TERT promoter mutations, combined with MRI‐derived and clinical features, revealed different survival subgroups with distinct responses to current treatments. Our results show that poor survival associated with TERT mutations was only observed in patients exhibiting high peritumoral edema, and increased survival associated with a wild‐type TERT promoter was only observed in young patients. MRI‐detected necrosis often indicates the presence of TERT promoter mutations.