Prognostic value of chloride channel accessory mRNA expression in colon cancer

Pan,Xiaohang; Wang,Qiaoqi; Xu,Chenfei; Yan,Ling; Pang,Sen; Gan,Jialiang

doi:10.3892/ol.2019.10615

Prognostic value of chloride channel accessory mRNA expression in colon cancer

Authors:
- Xiaohang Pan
- Qiaoqi Wang
- Chenfei Xu
- Ling Yan
- Sen Pang
- Jialiang Gan
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Affiliations: Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Medical Cosmetology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530000, P.R. China, Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: July 15, 2019 https://doi.org/10.3892/ol.2019.10615
Pages: 2967-2976
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chloride channel accessory (CLCA) is a gene family that encode Ca2+ activated chloride channels, which make a substantial contribution to various diseases. The aim of the present study was to investigate the prognostic value of CLCA expression in colon cancer. In an attempt to elucidate the value of CLCA mRNA expression in the prognosis of patients with colon cancer, the gene expression data of 438 patients with colon cancer were analyzed. The source of the data was The Cancer Genome Atlas, and it was identified that high expression levels of CLCA1 and CLCA2 were associated with a favorable overall survival (OS) time in patients with colon cancer. As revealed by joint effects analysis, the co‑occurrence of high expression levels of CLCA1 and CLCA2 was associated with a favorable OS time in patients with colon cancer. CLCA genes were investigated using gene set enrichment analysis. The results of the bioinformatics analysis demonstrated that high expression levels of CLCA1 and CLCA2 were associated with the prognosis of colon cancer. These findings suggest that CLCA1 and CLCA2 are potential prognostic biomarkers for patients with colon cancer. Furthermore, combining CLCA1 and CLCA2 can enhance the sensitivity of the prediction of the OS time of patients with colon cancer.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
2	Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R and Jemal A: Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 66:271–289. 2016. View Article : Google Scholar : PubMed/NCBI
3	Feo L, Polcino M and Nash GM: Resection of the primary tumor in stage IV colorectal cancer: When is it necessary? Surg Clin North Am. 97:657–669. 2017. View Article : Google Scholar : PubMed/NCBI
4	Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, van de Velde CJ and Watanabe T: Colorectal cancer. Nat Rev Dis Primers. 1:150652015. View Article : Google Scholar : PubMed/NCBI
5	Gruber AD, Elble RC, Ji HL, Schreur KD, Fuller CM and Pauli BU: Genomic cloning, molecular characterization, and functional analysis of human CLCA1, the first human member of the family of Ca2+-activated Cl-channel proteins. Genomics. 54:200–214. 1998. View Article : Google Scholar : PubMed/NCBI
6	Gandhi R, Elble RC, Gruber AD, Schreur KD, Ji HL, Fuller CM and Pauli BU: Molecular and functional characterization of a calcium-sensitive chloride channel from mouse lung. J Biol Chem. 273:32096–32101. 1998. View Article : Google Scholar : PubMed/NCBI
7	Pauli BU, Abdel-Ghany M, Cheng HC, Gruber AD, Archibald HA and Elble RC: Molecular characteristics and functional diversity of CLCA family members. Clin Exp Pharmacol Physiol. 27:901–905. 2000. View Article : Google Scholar : PubMed/NCBI
8	Loewen ME and Forsyth GW: Structure and function of CLCA proteins. Physiol Rev. 85:1061–1092. 2005. View Article : Google Scholar : PubMed/NCBI
9	Patel AC, Brett TJ and Holtzman MJ: The role of CLCA proteins in inflammatory airway disease. Annu Rev Physiol. 71:425–449. 2009. View Article : Google Scholar : PubMed/NCBI
10	Li X, Hu W, Zhou J, Huang Y, Peng J, Yuan Y, Yu J and Zheng S: CLCA1 suppresses colorectal cancer aggressiveness via inhibition of the Wnt/beta-catenin signaling pathway. Cell Commun Signal. 15:382017. View Article : Google Scholar : PubMed/NCBI
11	Yang B, Cao L, Liu B, McCaig CD and Pu J: The transition from proliferation to differentiation in colorectal cancer is regulated by the calcium activated chloride channel A1. PLoS One. 8:e608612013. View Article : Google Scholar : PubMed/NCBI
12	Gruber AD and Pauli BU: Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2. Cancer Res. 59:5488–5491. 1999.PubMed/NCBI
13	Sasaki Y, Koyama R, Maruyama R, Hirano T, Tamura M, Sugisaka J, Suzuki H, Idogawa M, Shinomura Y and Tokino T: CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion. Cancer Biol Ther. 13:1512–1521. 2012. View Article : Google Scholar : PubMed/NCBI
14	Agnel M, Vermat T and Culouscou JM: Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea. FEBS Lett. 455:295–301. 1999. View Article : Google Scholar : PubMed/NCBI
15	Yu Y, Walia V and Elble RC: Loss of CLCA4 promotes epithelial-to-mesenchymal transition in breast cancer cells. PLoS One. 8:e839432013. View Article : Google Scholar : PubMed/NCBI
16	Carithers LJ, Ardlie K, Barcus M, Branton PA, Britton A, Buia SA, Compton CC, DeLuca DS, Peter-Demchok J, Gelfand ET, et al: A novel approach to high-quality postmortem tissue procurement: The GTEx project. Biopreserv Biobank. 13:311–319. 2015. View Article : Google Scholar : PubMed/NCBI
17	Shaul YD, Yuan B, Thiru P, Nutter-Upham A, McCallum S, Lanzkron C, Bell GW and Sabatini DM: MERAV: A tool for comparing gene expression across human tissues and cell types. Nucleic Acids Res. 44(D1): D560–D566. 2016. View Article : Google Scholar : PubMed/NCBI
18	Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, Franz M, Grouios C, Kazi F, Lopes CT, et al: The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 38 (Web Server Issue). W214–W220. 2010. View Article : Google Scholar
19	Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009. View Article : Google Scholar : PubMed/NCBI
20	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
21	Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI
22	Pardo LA and Stühmer W: The roles of K(+) channels in cancer. Nat Rev Cancer. 14:39–48. 2014. View Article : Google Scholar : PubMed/NCBI
23	Cuddapah VA and Sontheimer H: Ion channels and transporters [corrected] in cancer. 2. Ion channels and the control of cancer cell migration. Am J Physiol Cell Physiol. 301:C541–C549. 2011. View Article : Google Scholar : PubMed/NCBI
24	Peretti M, Angelini M, Savalli N, Florio T, Yuspa SH and Mazzanti M: Chloride channels in cancer: Focus on chloride intracellular channel 1 and 4 (CLIC1 AND CLIC4) proteins in tumor development and as novel therapeutic targets. Biochim Biophys Acta. 1848:2523–2531. 2015. View Article : Google Scholar : PubMed/NCBI
25	Hoshino M, Morita S, Iwashita H, Sagiya Y, Nagi T, Nakanishi A, Ashida Y, Nishimura O, Fujisawa Y and Fujino M: Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway. Am J Respir Crit Care Med. 165:1132–1136. 2002. View Article : Google Scholar : PubMed/NCBI
26	Kim JA, Kang YS and Lee YS: Role of Ca2+-activated Cl-channels in the mechanism of apoptosis induced by cyclosporin A in a human hepatoma cell line. Biochem Biophys Res Commun. 309:291–297. 2003. View Article : Google Scholar : PubMed/NCBI
27	Walia V, Ding M, Kumar S, Nie D, Premkumar LS and Elble RC: hCLCA2 Is a p53-inducible inhibitor of breast cancer cell proliferation. Cancer Res. 69:6624–6632. 2009. View Article : Google Scholar : PubMed/NCBI
28	Bustin SA, Li SR and Dorudi S: Expression of the Ca2+-activated chloride channel genes CLCA1 and CLCA2 is downregulated in human colorectal cancer. DNA Cell Biol. 20:331–338. 2001. View Article : Google Scholar : PubMed/NCBI
29	Pelaseyed T, Bergström JH, Gustafsson JK, Ermund A, Birchenough GM, Schütte A, van der Post S, Svensson F, Rodríguez-Piñeiro AM, Nyström EE, et al: The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 260:8–20. 2014. View Article : Google Scholar : PubMed/NCBI
30	Nyström EEL, Birchenough GMH, van der Post S, Arike L, Gruber AD, Hansson GC and Johansson MEV: Calcium-activated chloride channel regulator 1 (CLCA1) controls mucus expansion in colon by proteolytic activity. EBioMedicine. 33:134–143. 2018. View Article : Google Scholar : PubMed/NCBI
31	Yang B, Cao L, Liu J, Xu Y, Milne G, Chan W, Heys SD, McCaig CD and Pu J: Low expression of chloride channel accessory 1 predicts a poor prognosis in colorectal cancer. Cancer. 121:1570–1580. 2015. View Article : Google Scholar : PubMed/NCBI
32	Ramena G, Yin Y, Yu Y, Walia V and Elble RC: CLCA2 interactor EVA1 is required for mammary epithelial cell differentiation. PLoS One. 11:e01474892016. View Article : Google Scholar : PubMed/NCBI
33	Sharma A, Ramena G, Yin Y, Premkumar L and Elble RC: CLCA2 is a positive regulator of store-operated calcium entry and TMEM16A. PLoS One. 13:e01965122018. View Article : Google Scholar : PubMed/NCBI
34	Kruse JP and Gu W: Modes of p53 regulation. Cell. 137:609–622. 2009. View Article : Google Scholar : PubMed/NCBI
35	Tanikawa C, Nakagawa H, Furukawa Y, Nakamura Y and Matsuda K: CLCA2 as a p53-inducible senescence mediator. Neoplasia. 14:141–149. 2012. View Article : Google Scholar : PubMed/NCBI
36	Herr HW and Donat SM: Prostatic tumor relapse in patients with superficial bladder tumors: 15-year outcome. J Urol. 161:1854–1857. 1999. View Article : Google Scholar : PubMed/NCBI
37	Lu CY, Uen YH, Tsai HL, Chuang SC, Hou MF, Wu DC, Juo SH, Lin SR and Wang JY: Molecular detection of persistent postoperative circulating tumour cells in stages II and III colon cancer patients via multiple blood sampling: Prognostic significance of detection for early relapse. Br J Cancer. 104:1178–1184. 2011. View Article : Google Scholar : PubMed/NCBI
38	Barrier A, Lemoine A, Boelle PY, Tse C, Brault D, Chiappini F, Breittschneider J, Lacaine F, Houry S, Huguier M, et al: Colon cancer prognosis prediction by gene expression profiling. Oncogene. 24:6155–6164. 2005. View Article : Google Scholar : PubMed/NCBI