A three ion channel genes-based signature predicts prognosis of primary glioblastoma patients and reveals a chemotherapy sensitive subtype
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Hao-Yuan Wang1,2,4,5,*, Ji-Ye Li3,4,*, Xiu Liu7, Xiao-Yan Yan4,5, Wen Wang3,5, Fan Wu4,5, Ting-Yu Liang4,5, Fan Yang4,5, Hui-Min Hu4,5, Heng-Xu Mao1,2, Yan-Wei Liu5,6, Shi-Zhong Zhang1,2
1Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
2The 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
3Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
4Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
5Chinese Glioma Cooperative Group (CGCG), Beijing, China
6Department of Radiation Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
7Center for Brain Disorders Research, Capital Medical University, Beijing, China
*These authors contributed equally to this work
Shi-Zhong Zhang, email: email@example.com
Yan-Wei Liu, email: firstname.lastname@example.org
Keywords: alpha-fetoprotein, antigen epitope, heat shock protein 70, functional peptide, immunity
Received: August 10, 2016 Accepted: September 29, 2016 Published: October 04, 2016
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.
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