title: A three ion channel genes-based signature predicts prognosis of primary glioblastoma patients and reveals a chemotherapy sensitive subtype.
abstract: Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of brain tumor. However, the roles of ion channels in glioma remain controversial. In the present study, we systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using RNAseq expression profiling. First, a molecular signature comprising three ion channel genes (KCNN4, KCNB1 and KCNJ10) was identified using Univariate Cox regression and two-tailed student's t test conducted in overall survival (OS) and gene expression. We assigned a risk score based on three ion channel genes to each primary Glioblastoma multiforme (pGBM) patient. We demonstrated that pGBM patients who had a high risk of unfavorable outcome were sensitive to chemotherapy. Next, we screened the three ion genes-based signature in different molecular glioma subtypes. The signature showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis for the functional annotation of the signature showed that patients with high-risk scores tended to exhibit the increased expression of proteins associated with apoptosis, immune response, cell adhesion and motion and vasculature development. Gene Set Enrichment Analysis (GSEA) results showed that pathways associated with negative regulation of programmed cell death, cell proliferation and locomotory behavior were highly expressed in the high-risk group. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial, Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Hao-Yuan
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Li
authors.affiliation: Center for Brain Disorders Research, Capital Medical University, Beijing, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Liang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Cooperative Group (CGCG), Beijing, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial, Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Heng-Xu
authors.initials: HX
authors.lastname: Mao
authors.affiliation: Chinese Glioma Cooperative Group (CGCG), Beijing, China.|Department of Radiation Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.|The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial, Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shi-Zhong
authors.initials: SZ
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D003131:Combined Modality Therapy; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D058977:Molecular Sequence Annotation; D011379:Prognosis; D016016:Proportional Hazards Models; D059467:Transcriptome; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D007473:Ion Channels
keywords: alpha-fetoprotein; antigen epitope; functional peptide; heat shock protein 70; immunity