Transcriptional Characteristics of IDH-Wild Type Glioma Subgroups Highlight the Biological Processes Underlying Heterogeneity of IDH-Wild Type WHO Grade IV Gliomas

摘要: Isocitric dehydrogenase (IDH)-wild type diffuse gliomas, which have a poorer prognosis than their IDH-mutant counterparts, are also accompanied with high heterogeneity. Here, we aimed to identify the key biological processes associated three groups of IDH-wild gliomas in 323 patients. By The Consortium Inform Molecular and Practical Approaches CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommendation, Group A, astrocytic glioma, World Health Organization (WHO) grade II/III; B, one (or more) genetic alterations: TERT promoter mutation, EGFR gene amplification, gain chromosome 7 combined loss 10, WHO IV; C, glioblastoma, IV. Consistent histologic molecular features, successfully identified that activities "cell cycle" mitosis" significantly elevated B compared A; microenvironment-related hallmarks "angiogenesis" "hypoxia," "extracellular matrix," "immune response," "positive regulation transcriptional activities" were more enriched C B. We constructed nine-gene signature from differentially expressed genes among further stratify IV (Groups C) whose survival cannot be clearly stratified by current classification systems. This was an independent factor for had better prognostic value other known factors both training validation dataset. In addition, risk score positively correlated amount infiltrated immune cells, expression checkpoints, cycle," matrix." bioinformatic analysis results validated immunohistochemistry patient-derived cell proliferation assay. Overall, our findings revealed underlying new classifications glioma. Meanwhile, signature, could properly prognosis, activates, extracellular matrix-mediated activities, immune-microenvironment gliomas.