FXYD6 is a new biomarker of cholangiocarcinoma

Chen,Xiongfei; Sun,Mingzhu; Hu,Yazhuo; Zhang,Honghong; Wang,Zhanbo; Zhou,Ningxin; Yan,Xinyun

doi:10.3892/ol.2013.1727

FXYD6 is a new biomarker of cholangiocarcinoma

Authors:
- Xiongfei Chen
- Mingzhu Sun
- Yazhuo Hu
- Honghong Zhang
- Zhanbo Wang
- Ningxin Zhou
- Xinyun Yan
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Affiliations: Medical College of Soochow University, Industrial Park, Suzhou, Jiangsu 215123, P.R. China, Department of Pathology, General Hospital of PLA Second Artillery, Beijing 100888, P.R. China, Institute of Geriatrics, PLA General Hospital, Beijing 100853, P.R. China, Department of Pathology, PLA General Hospital, Beijing 100853, P.R. China, Institute of Hepatobiliary Gastrointestinal Disease, General Hospital of PLA Second Artillery, Beijing 100088, P.R. China, Key Laboratory of Protein and Peptide Pharmaceuticals, CAS‑University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China
Published online on: December 4, 2013 https://doi.org/10.3892/ol.2013.1727
Pages: 393-398

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Abstract

Members of the FXYD domain‑containing ion transport regulator protein family, including FXYD3 and FXYD5, play an important role in the pathogenesis of numerous tumors. However, the correlation between the expression of FXYD6 and tumors remains poorly understood. In the current study, the expression of FXYD6 was examined immunohistochemically in 72 cholangiocarcinoma tissues and 30 distal normal bile duct tissues matched with the tumors. The results show that the positive expression rate of FXYD6 was significantly higher in cholangiocarcinoma than that in normal bile duct tissue (69 vs. 33.3%; P=0.002). Furthermore, the positive expression rate of FXYD6 in well‑ and moderately‑differentiated cholangiocarcinoma was clearly higher than that in poorly‑differentiated and mucinous cholangiocarcinoma (85.7 vs. 40%; P=0.000). However, there was no significant correlation between the expression of FXYD6 and gender (P=0.393), age (P=0.174), histological type (P=0.123), T stage (P=0.164), lymph node metastasis (P=0.343), perineural invasion (P=0.088) and tumor location (P=0.238). The results of this study indicate that FXYD6 may be a new biomarker for cholangiocarcinoma and may be associated with a favorable prognosis in this malignant disease.

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1	Marsh RW, Alonxo M, Bajaj S, et al: Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part II: multidisciplinary management. J Surg Oncol. 106:339–345. 2012. View Article : Google Scholar
2	Khan SA, Davidson BR, Goldin RD, et al: Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update. Gut. 61:1657–1669. 2012. View Article : Google Scholar : PubMed/NCBI
3	Briggs CD, Neal CP, Mann CD, Steward WP, Manson MM and Berry DP: Prognostic molecular markers in cholangiocarcinoma: a systematic review. Eur J Cancer. 45:33–47. 2009. View Article : Google Scholar : PubMed/NCBI
4	Delprat B, Schaer D, Roy S, Wang J, Puel JL and Geering K: FXYD6 is a novel regulator of Na, K-ATPase expressed in the inner ear. J Biol Chem. 282:7450–7456. 2007. View Article : Google Scholar : PubMed/NCBI
5	Zhu ZL, Zhao ZR, Zhang Y, et al: Expression and significance of FXYD-3 protein in gastric adenocarcinoma. Dis Markers. 28:63–69. 2010. View Article : Google Scholar : PubMed/NCBI
6	Kayed H, Kleeff J, Kolb A, et al: FXYD3 is overexpressed in pancreatic ductal adenocarcinoma and influences pancreatic cancer cell growth. Int J Cancer. 118:43–54. 2006. View Article : Google Scholar : PubMed/NCBI
7	Wang MW, Gu P, Zhang ZY, et al: FXYD3 expression in gliomas and its clinicopathological significance. Oncol Res. 18:133–139. 2009. View Article : Google Scholar : PubMed/NCBI
8	Maehata Y, Hirahashi M, Aishima S, et al: Significance of dysadherin and E-cadherin expression in differentiated-type gastric carcinoma with submucosal invasion. Hum Pathol. 42:558–567. 2011. View Article : Google Scholar : PubMed/NCBI
9	Kadowaki K, Sugimoto K, Yamaguchi F, Song T, Watanabe Y, Singh K and Tokuda M: Phosphohippolin expression in the rat central nervous system. Brain Res Mol Brain Res. 125:105–112. 2004. View Article : Google Scholar : PubMed/NCBI
10	Shiina N, Yamaguchi K and Tokunaga M: RNG105 deficiency impairs the dendritic localization of mRNAs for Na⁺/K⁺ ATPase subunit isoforms and leads to the degeneration of neuronal networks. J Neurosci. 30:12816–12830. 2010. View Article : Google Scholar : PubMed/NCBI
11	Olstad OK, Gautvik VT, Reppe S, et al: Molecular heterogeneity in human osteosarcoma demonstrated by enriched mRNAs isolated by directional tag PCR subtraction cloning. Anticancer Res. 23:2201–2216. 2003.
12	Xiao M, Zhou NX, Gao LJ, et al: A study on expression of human gene fxyd6 in bile duct benign and malignant tumors by RT-PCR. Chin J Bases Clin General Sur. 15:223–225. 2007.(In Chinese).
13	Liu J, Zhou N and Zhang X: A monoclonal antibody against human FXYD6. Hybridoma (Larchmt). 30:487–490. 2011. View Article : Google Scholar : PubMed/NCBI
14	Geering K: FXYD proteins: new regulators of Na-K-ATPase. Am J Physiol Renal PhysSiol. 290:F241–F250. 2006. View Article : Google Scholar : PubMed/NCBI
15	Saxena A, Chua TC, Chu FC and Morris DL: Improved outcomes after aggressive surgical resection of hilar cholangiocarcinoma: a critical analysis of recurrence and survival. Am J Surg. 202:310–320. 2011. View Article : Google Scholar
16	Nakanuma Y, Sato Y, Harada K, Sasaki M, Xu J and Ikeda H: Pathological classification of intrahepatic cholangiocarcinoma based on a new concept. World J Hepatol. 2:419–427. 2010. View Article : Google Scholar : PubMed/NCBI
17	Ito Y, Nakamura Y, Takahashi N, et al: A genetic association study of the FXYD domain containing ion transport regulator 6 (FXYD6) gene, encoding phosphohippolin, in susceptibility to schizophrenia in a Japanese population. Neurosci Lett. 438:70–75. 2008. View Article : Google Scholar
18	Iwata Y, Yamada K, Iwayama Y, et al: Failure to confirm genetic association of the FXYD6 gene with schizophrenia: the Japanese population and meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 153B:1221–1227. 2010.PubMed/NCBI
19	Zhong N, Zhang R, Qiu C, et al: A novel replicated association between FXYD6 gene and schizophrenia. Biochem Biophys Res Commun. 405:118–121. 2011. View Article : Google Scholar : PubMed/NCBI
20	Shen FZ, Zhang BY, Feng YJ, et al: Current research in perineural invasion of cholangiocarcinoma. J Exp Clin Cancer Res. 29:242010. View Article : Google Scholar : PubMed/NCBI
21	Shindo Y, Morishita K, Kotake E, et al: FXYD6, a Na, K-ATPase regulator, is expressed in type II taste cells. Biosci Biotechnol Biochem. 75:1061–1066. 2011. View Article : Google Scholar : PubMed/NCBI
22	Rajasekaran SA, Huynh TP, Wolle DG, et al: Na, K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis. Mol Cancer Ther. 9:1515–1524. 2010. View Article : Google Scholar : PubMed/NCBI
23	Tummala R, Wolle D, Barwe SP, Sampson VB, Rajasekaran AK and Pendyala L: Expression of Na, K-ATPase-beta(1) subunit increases uptake and sensitizes carcinoma cells to oxaliplatin. Cancer Chemother Pharmacol. 64:1187–1194. 2009. View Article : Google Scholar : PubMed/NCBI
24	Mijatovic T, Ingrassia L, Facchini V and Kiss R: Na⁺/K⁺-ATPase alpha subunits as new targets in anticancer therapy. Expert Opin Ther Targets. 12:1403–1417. 2008.
25	Seligson DB, Rajasekaran SA, Yu H, et al: Na, K-adenosine triphosphatase alpha1-subunit predicts survival of renal clear cell carcinoma. J Urol. 179:338–345. 2008. View Article : Google Scholar : PubMed/NCBI