A glycolysis-based ten-gene signature correlates with the clinical outcome, molecular subtype and IDH1 mutation in glioblastoma. (20th November 2017)

• Record Type: Journal Article
• Authors: Chen, Cong; Shi, Yu; Li, Yong; He, Zhi-Cheng; Zhou, Kai; Zhang, Xiao-Ning; Yang, Kai-Di; Wu, Jin-Rong; Kung, Hsiang-Fu; Ping, Yi-Fang; Bian, Xiu-Wu
• Is Part Of: Journal of genetics and genomics. Volume 44:Number 11(2017)
• Page Start: 519
• Page End: 530
• Publication Date: 2017-11-20
• Subjects: Glycolysis -- Glioblastoma -- Prognosis -- IDH1 -- Molecular subtype; GBM glioblastoma -- G-CIMP glioma-CpG island methylator phenotype -- GGESS glycolytic gene expression signature score -- IDH1 isocitrate dehydrogenase 1 -- REMBRANDT Repository for Molecular Brain Neoplasia Data -- TCGA The Cancer Genome Atlas; Genetics -- Periodicals; Genomics -- Periodicals; 576.505
• DOI: 10.1016/j.jgg.2017.05.007
• Languages: English
• ISSNs: 1673-8527

Abstract

Abstract: Reprogrammed metabolism is a hallmark of cancer. Glioblastoma (GBM) tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical significance of glycolysis and its underlying relations with the molecular features such as IDH1 mutation and subtype have not been elucidated yet. Herein, based on glioma datasets including TCGA (The Cancer Genome Atlas), REMBRANDT (Repository for Molecular Brain Neoplasia Data) and GSE16011, we established a glycolytic gene expression signature score (GGESS) by incorporating ten glycolytic genes. Then we performed survival analyses and investigated the correlations between GGESS and IDH1 mutation as well as the molecular subtypes in GBMs. The results showed that GGESS independently predicted unfavorable prognosis and poor response to chemotherapy of GBM patients. Notably, GGESS was high in GBMs of mesenchymal subtype but low in IDH1 -mutant GBMs. Furthermore, we found that the promoter regions of tumor-promoting glycolytic genes were hypermethylated in IDH1 -mutant GBMs. Finally, we found that high GGESS also predicted poor prognosis and poor response to chemotherapy when investigating IDH1 -wildtype GBM patients only. Collectively, glycolysis represented by GGESS predicts unfavorable clinical outcome of GBM patients and is closely associated with mesenchymal subtype and IDH1 mutation in GBMs.