Skip to main content
Top
Published in: Journal of Neuro-Oncology 2/2017

01-09-2017 | Clinical Study

Prognostic value of ion channel genes in Chinese patients with gliomas based on mRNA expression profiling

Authors: Feng-fei Lu, Hao-Yuan Wang, Xiao-zheng He, Ting-Yu Liang, Wen Wang, Hui-Min Hu, Fan Wu, Yan-Wei Liu, Shi-Zhong Zhang

Published in: Journal of Neuro-Oncology | Issue 2/2017

Login to get access

Abstract

Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of human cancer. However, the roles of ion channels in glioma remain controversial. We systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using whole-genome mRNA expression profiling. First, a molecular signature comprising 47 ion channel genes (IC47) was identified using Spearman’s rank correlation test conducted between tumor grade and gene expression. We assigned a risk score based on IC47 to each glioma patient. We demonstrated that the risk score effectively predicted overall survival in glioma patients. Next, we screened IC47 in different molecular glioma subtypes. IC47 showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis and gene set variation analysis (GSVA) for the functional annotation of IC47 showed that patients with high-risk scores tended to exhibit the decreased expression of proteins associated with the apoptosis and cell adhesion, and higher expression of proteins associated with the cell cycle and cell proliferation. 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.
Appendix
Available only for authorised users
Literature
2.
go back to reference Fiske JL, Fomin VP, Brown ML, Duncan RL, Sikes RA (2006) Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev 25(3):493–500CrossRefPubMed Fiske JL, Fomin VP, Brown ML, Duncan RL, Sikes RA (2006) Voltage-sensitive ion channels and cancer. Cancer Metastasis Rev 25(3):493–500CrossRefPubMed
3.
go back to reference Camerino DC, Tricarico D, Desaphy JF (2007) Ion channel pharmacology. Neurotherapeutics 4(2):184–198CrossRefPubMed Camerino DC, Tricarico D, Desaphy JF (2007) Ion channel pharmacology. Neurotherapeutics 4(2):184–198CrossRefPubMed
4.
go back to reference Schwab A, Fabian A, Hanley PJ, Stock C (2012) Role of ion channels and transporters in cell migration. Physiol Rev 92(4):1865–1913CrossRefPubMed Schwab A, Fabian A, Hanley PJ, Stock C (2012) Role of ion channels and transporters in cell migration. Physiol Rev 92(4):1865–1913CrossRefPubMed
6.
go back to reference Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D (1997) GeneCards: integrating information about genes, proteins and diseases. Trends Genet 13(4):163CrossRefPubMed Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D (1997) GeneCards: integrating information about genes, proteins and diseases. Trends Genet 13(4):163CrossRefPubMed
7.
go back to reference Li M, Xiong ZG. Ion channels as targets for cancer therapy. Int J Physiol Pathophysiol Pharmacol 3(2):156–166 Li M, Xiong ZG. Ion channels as targets for cancer therapy. Int J Physiol Pathophysiol Pharmacol 3(2):156–166
8.
9.
go back to reference Pardo LA, Contreras-Jurado C, Zientkowska M, Alves F, Stuhmer W (2005) Role of voltage-gated potassium channels in cancer. J Membr Biol 205(3):115–124CrossRefPubMed Pardo LA, Contreras-Jurado C, Zientkowska M, Alves F, Stuhmer W (2005) Role of voltage-gated potassium channels in cancer. J Membr Biol 205(3):115–124CrossRefPubMed
10.
go back to reference Le GJY, Ouadid-Ahidouch H, Soriani O, Besson P, Ahidouch A, Vandier C (2007) Voltage-gated ion channels, new targets in anti-cancer research. Recent Pat Anticancer Drug Discov 2(3):189–202CrossRef Le GJY, Ouadid-Ahidouch H, Soriani O, Besson P, Ahidouch A, Vandier C (2007) Voltage-gated ion channels, new targets in anti-cancer research. Recent Pat Anticancer Drug Discov 2(3):189–202CrossRef
11.
12.
go back to reference Zhang WM, Zhou J, Ye QJ (2008) Endothelin-1 enhances proliferation of lung cancer cells by increasing intracellular free Ca2+. Life Sci 82(13–14):764–771CrossRefPubMed Zhang WM, Zhou J, Ye QJ (2008) Endothelin-1 enhances proliferation of lung cancer cells by increasing intracellular free Ca2+. Life Sci 82(13–14):764–771CrossRefPubMed
13.
go back to reference Ma YG, Liu WC, Dong S et al (2012) Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells. PLoS ONE 7(5):e37451CrossRefPubMedPubMedCentral Ma YG, Liu WC, Dong S et al (2012) Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells. PLoS ONE 7(5):e37451CrossRefPubMedPubMedCentral
14.
go back to reference Stupp R, Hegi ME, van den Bent MJ et al (2006) Changing paradigms–an update on the multidisciplinary management of malignant glioma. Oncologist 11(2):165–180CrossRefPubMed Stupp R, Hegi ME, van den Bent MJ et al (2006) Changing paradigms–an update on the multidisciplinary management of malignant glioma. Oncologist 11(2):165–180CrossRefPubMed
15.
go back to reference Giese A, Bjerkvig R, Berens ME, Westphal M (2003) Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21(8):1624–1636CrossRefPubMed Giese A, Bjerkvig R, Berens ME, Westphal M (2003) Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21(8):1624–1636CrossRefPubMed
18.
go back to reference Sciaccaluga M, Fioretti B, Catacuzzeno L et al (2010) CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity. Am J Physiol Cell Physiol 299(1):C175–C184CrossRefPubMed Sciaccaluga M, Fioretti B, Catacuzzeno L et al (2010) CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity. Am J Physiol Cell Physiol 299(1):C175–C184CrossRefPubMed
19.
go back to reference Catacuzzeno L, Aiello F, Fioretti B et al (2011) Serum-activated K and Cl currents underlay U87-MG glioblastoma cell migration. J Cell Physiol 226(7):1926–1933CrossRefPubMed Catacuzzeno L, Aiello F, Fioretti B et al (2011) Serum-activated K and Cl currents underlay U87-MG glioblastoma cell migration. J Cell Physiol 226(7):1926–1933CrossRefPubMed
20.
go back to reference Cuddapah VA, Turner KL, Seifert S, Sontheimer H (2013) Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3.1 and ClC-3. J Neurosci 33(4):1427–1440CrossRefPubMedPubMedCentral Cuddapah VA, Turner KL, Seifert S, Sontheimer H (2013) Bradykinin-induced chemotaxis of human gliomas requires the activation of KCa3.1 and ClC-3. J Neurosci 33(4):1427–1440CrossRefPubMedPubMedCentral
21.
go back to reference Garzon-Muvdi T, Schiapparelli P, ap Rhys C et al. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation. PLoS Biol 10(5):e1001320 Garzon-Muvdi T, Schiapparelli P, ap Rhys C et al. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation. PLoS Biol 10(5):e1001320
22.
go back to reference Yan W, Zhang W, You G et al (2012) Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group. Neuro Oncol 14(12):1432–1440CrossRefPubMedPubMedCentral Yan W, Zhang W, You G et al (2012) Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group. Neuro Oncol 14(12):1432–1440CrossRefPubMedPubMedCentral
23.
go back to reference Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D (1998) GeneCards: a novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics 14(8):656–664CrossRefPubMed Rebhan M, Chalifa-Caspi V, Prilusky J, Lancet D (1998) GeneCards: a novel functional genomics compendium with automated data mining and query reformulation support. Bioinformatics 14(8):656–664CrossRefPubMed
24.
go back to reference Sharman JL, Mpamhanga CP, Spedding M et al (2011) IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data. Nucleic Acids Res 39(Database issue):D534–D538CrossRefPubMed Sharman JL, Mpamhanga CP, Spedding M et al (2011) IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data. Nucleic Acids Res 39(Database issue):D534–D538CrossRefPubMed
25.
go back to reference Huang dW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57 Huang dW, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57
27.
go back to reference Phillips HS, Kharbanda S, Chen R et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9(3):157–173CrossRefPubMed Phillips HS, Kharbanda S, Chen R et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9(3):157–173CrossRefPubMed
28.
go back to reference Bao ZS, Li MY, Wang JY et al (2014) Prognostic value of a nine-gene signature in glioma patients based on mRNA expression profiling. CNS Neurosci Ther 20(2):112–118CrossRefPubMed Bao ZS, Li MY, Wang JY et al (2014) Prognostic value of a nine-gene signature in glioma patients based on mRNA expression profiling. CNS Neurosci Ther 20(2):112–118CrossRefPubMed
29.
go back to reference Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53(8):799–808CrossRefPubMed Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53(8):799–808CrossRefPubMed
30.
go back to reference Kang SS, Han KS, Ku BM et al (2010) Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival. Cancer Res 70(3):1173–1183CrossRefPubMedPubMedCentral Kang SS, Han KS, Ku BM et al (2010) Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival. Cancer Res 70(3):1173–1183CrossRefPubMedPubMedCentral
31.
go back to reference Bomben VC, Turner KL, Barclay TT, Sontheimer H (2011) Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas. J Cell Physiol 226(7):1879–1888CrossRefPubMed Bomben VC, Turner KL, Barclay TT, Sontheimer H (2011) Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas. J Cell Physiol 226(7):1879–1888CrossRefPubMed
32.
go back to reference Ko JH, Ko EA, Gu W, Lim I, Bang H, Zhou T (2013) Expression profiling of ion channel genes predicts clinical outcome in breast cancer. Mol Cancer 12(1):106CrossRefPubMedPubMedCentral Ko JH, Ko EA, Gu W, Lim I, Bang H, Zhou T (2013) Expression profiling of ion channel genes predicts clinical outcome in breast cancer. Mol Cancer 12(1):106CrossRefPubMedPubMedCentral
33.
go back to reference Ko JH, Gu W, Lim I, Bang H, Ko EA, Zhou T (2014) Ion channel gene expression in lung adenocarcinoma: potential role in prognosis and diagnosis. PLoS ONE 9(1):e86569CrossRefPubMedPubMedCentral Ko JH, Gu W, Lim I, Bang H, Ko EA, Zhou T (2014) Ion channel gene expression in lung adenocarcinoma: potential role in prognosis and diagnosis. PLoS ONE 9(1):e86569CrossRefPubMedPubMedCentral
34.
go back to reference Liu X, Chang Y, Reinhart PH, Sontheimer H, Chang Y (2002) Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells. J Neurosci 22(5):1840–1849PubMed Liu X, Chang Y, Reinhart PH, Sontheimer H, Chang Y (2002) Cloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells. J Neurosci 22(5):1840–1849PubMed
36.
37.
go back to reference D’Alessandro G, Catalano M, Sciaccaluga M et al. (2013) KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo. Cell Death Dis 4:e773CrossRefPubMedPubMedCentral D’Alessandro G, Catalano M, Sciaccaluga M et al. (2013) KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in vivo. Cell Death Dis 4:e773CrossRefPubMedPubMedCentral
38.
go back to reference Britschgi A, Bill A, Brinkhaus H et al (2013) Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling. Proc Natl Acad Sci USA 110(11):E1026–E1034CrossRefPubMedPubMedCentral Britschgi A, Bill A, Brinkhaus H et al (2013) Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling. Proc Natl Acad Sci USA 110(11):E1026–E1034CrossRefPubMedPubMedCentral
39.
go back to reference Deng YJ, Tang N, Liu C et al (2014) CLIC4, ERp29, and Smac/DIABLO derived from metastatic cancer stem-like cells stratify prognostic risks of colorectal cancer. Clin Cancer Res 20(14):3809–3817CrossRefPubMed Deng YJ, Tang N, Liu C et al (2014) CLIC4, ERp29, and Smac/DIABLO derived from metastatic cancer stem-like cells stratify prognostic risks of colorectal cancer. Clin Cancer Res 20(14):3809–3817CrossRefPubMed
40.
go back to reference Wang XT, Nagaba Y, Cross HS, Wrba F, Zhang L, Guggino SE (2000) The mRNA of l-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon. Am J Pathol 157(5):1549–1562CrossRefPubMedPubMedCentral Wang XT, Nagaba Y, Cross HS, Wrba F, Zhang L, Guggino SE (2000) The mRNA of l-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon. Am J Pathol 157(5):1549–1562CrossRefPubMedPubMedCentral
42.
go back to reference Ding X, He Z, Zhou K et al (2010) Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J Natl Cancer Inst 102(14):1052–1068CrossRefPubMed Ding X, He Z, Zhou K et al (2010) Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J Natl Cancer Inst 102(14):1052–1068CrossRefPubMed
43.
go back to reference Ishiuchi S, Tsuzuki K, Yoshida Y et al (2002) Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells. Nat Med 8(9):971–978CrossRefPubMed Ishiuchi S, Tsuzuki K, Yoshida Y et al (2002) Blockage of Ca(2+)-permeable AMPA receptors suppresses migration and induces apoptosis in human glioblastoma cells. Nat Med 8(9):971–978CrossRefPubMed
44.
go back to reference Lyons SA, Chung WJ, Weaver AK, Ogunrinu T, Sontheimer H (2007) Autocrine glutamate signaling promotes glioma cell invasion. Cancer Res 67(19):9463–9471CrossRefPubMedPubMedCentral Lyons SA, Chung WJ, Weaver AK, Ogunrinu T, Sontheimer H (2007) Autocrine glutamate signaling promotes glioma cell invasion. Cancer Res 67(19):9463–9471CrossRefPubMedPubMedCentral
45.
go back to reference Arcangeli A, Crociani O, Lastraioli E, Masi A, Pillozzi S, Becchetti A (2009) Targeting ion channels in cancer: a novel frontier in antineoplastic therapy. Curr Med Chem 16(1):66–93CrossRefPubMed Arcangeli A, Crociani O, Lastraioli E, Masi A, Pillozzi S, Becchetti A (2009) Targeting ion channels in cancer: a novel frontier in antineoplastic therapy. Curr Med Chem 16(1):66–93CrossRefPubMed
46.
go back to reference Brisson L, Gillet L, Calaghan S et al (2011) Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene 30(17):2070–2076CrossRefPubMed Brisson L, Gillet L, Calaghan S et al (2011) Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae. Oncogene 30(17):2070–2076CrossRefPubMed
Metadata
Title
Prognostic value of ion channel genes in Chinese patients with gliomas based on mRNA expression profiling
Authors
Feng-fei Lu
Hao-Yuan Wang
Xiao-zheng He
Ting-Yu Liang
Wen Wang
Hui-Min Hu
Fan Wu
Yan-Wei Liu
Shi-Zhong Zhang
Publication date
01-09-2017
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 2/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-017-2539-0

Other articles of this Issue 2/2017

Journal of Neuro-Oncology 2/2017 Go to the issue