title: Identification of a five B cell-associated gene prognostic and predictive signature for advanced glioma patients harboring immunosuppressive subtype preference.
abstract: High grade gliomas contribute to most brain tumor mortality. A few studies reported that the immune system affected glioma development, and immune biomarkers helped understand the disease and formulate effective immunotherapy for patients. Currently, no B lymphocyte-based prognostic signature was reported in gliomas. By applying 78 B cell lineage-specific genes, we conducted a whole-genome gene expression analysis in 782 high grade gliomas derived from three independent datasets by Cox regression analysis and risk score method for signature identification, and then used Gene Ontology, Gene Set Enrichment Analysis, and other statistical methods for functional annotations of the signature-defined differences. We developed a five B cell-associated gene signature for prognosis of high grade glioma patients, which is independent of clinicopathological and genetic features. The signature identified high risk patients suitable for chemoradiotherapy, whereas low risk patients should rule out chemotherapy with radiotherapy only. We found that tumors of TCGA Mesenchymal subtype and wild type IDH1 were preferentially stratified to the high risk group, which bore strong immunosuppressive microenvironment, while tumors of TCGA Proneural subtype and mutated IDH1 were significantly accumulated to the low risk group, which exhibited less immunosuppressive state. The five B cell-associated gene signature predicts poor survival of high risk patients bearing strong immunosuppression and helps select optimal therapeutic regimens for glioma patients.
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, TiantanXili, Dongcheng District, Beijing 100050, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, TiantanXili, Dongcheng District, Beijing 100050, China.|Beijing Institute for Brain Disorders, Youanmen, Beijing, 100069, China.|Center for Brain Disorders Research, Capital Medical University, Youanmen, Beijing, 100069, China.
authors.forename: Jiye
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, TiantanXili, Dongcheng District, Beijing 100050, China.|Beijing Institute for Brain Disorders, Youanmen, Beijing, 100069, China.|Center for Brain Disorders Research, Capital Medical University, Youanmen, Beijing, 100069, China.
authors.forename: Sonya Wei
authors.initials: SW
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D003131:Combined Modality Therapy; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D060787:Neoplasm Grading; D009928:Organ Specificity / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarker; glioma; immune system; prognosis; tumor-infiltrating B cells