title: A five-miRNA signature with prognostic and predictive value for MGMT promoter-methylated glioblastoma patients.
abstract: Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profiles. The present study aimed to refine the prognostic and predictive value of MGMT promoter status in GBM by identifying a micro (mi)RNA risk signature. Data from The Cancer Genome Atlas was used for this study, with MGMT promoter-methylated samples randomly divided into training and internal validation sets. Data from The Chinese Glioma Genome Atlas was used for independent validation. A five miRNA-based risk signature was established for MGMT promoter-methylated GBM to distinguish cases as high- or low-risk with distinct prognoses, which was confirmed using internal and external validation sets. Importantly, the prognostic value of the signature was significant in different cohorts stratified by clinicopathologic factors and alkylating chemotherapy, and a multivariate Cox analysis found it to be an independent prognostic marker along with age and chemotherapy. Based on these three factors, we developed a quantitative model with greater accuracy for predicting the 1-year survival of patients with MGMT promoter-methylated GBM. These results indicate that the five-miRNA signature is an independent risk predictor for GBM with MGMT promoter methylation and can be used to identify patients at high risk of unfavorable outcome and resistant to alkylating chemotherapy, underscoring its potential for personalized GBM management.
authors: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
authors: Wen
authors: W
authors: Cheng
authors: Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, China.
authors: Xiufang
authors: X
authors: Ren
authors: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors: Jinquan
authors: J
authors: Cai
authors: Beijing Neurosurgical Institute, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Chuanbao
authors: C
authors: Zhang
authors: Beijing Neurosurgical Institute, Beijing, China.|Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Mingyang
authors: M
authors: Li
authors: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Kuanyu
authors: K
authors: Wang
authors: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
authors: Yang
authors: Y
authors: Liu
authors: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
authors: Sheng
authors: S
authors: Han
authors: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China.
authors: Anhua
authors: A
authors: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016009:Chi-Square Distribution; D002648:Child; D002681:China; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: MGMT promoter methylation; glioblastoma; miRNA; predictive model; prognosis