Expression of FXYD6 in Hilar Cholangiocarcinoma Tissue and Its Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHENXiong-fei ^1,2 , ZHOUNing-xin ³ , ZHANGHong-hong ⁴

1. Department of General Surgery, Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China;
2. Medical College of Soochow University, Suzhou 215123, Jiangsu Province, China;
3. Department of Hepatobiliary Surgery, General Hospital of PLA Rocket Forces, Beijing 100088, China;
4. Institute of Geriatrics, PLA General Hospital, Beijing 100853, China;

Corresponding author：

CHENXiong-fei, Email: chenxiongfei86@126.com

Keywords：

FXYD6; Hilar cholangiocarcinoma; Biomarker; Differentiation degree

DOI：

10.7507/1007-9424.20160344

Video：

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Objective To detect expression of FXYD6 protein in hilar cholangiocarcinoma tissues and explore its significances. Methods The expressions of FXYD6 protein in the 58 hilar cholangiocarcinoma tissues and 30 normal bile duct tissues adjacent to cancer were detected by strept avidin-biotin complex (SABC) immunohistochemistry. The relation between FXYD6 protein expression and biological characteristics of patient with hilar cholangiocarcinoma was analyzed. Results The positive rate of FXYD6 protein expression in the hilar cholangiocarcinoma tissues was significantly higher than that in the normal bile duct tissues adjacent to cancer[75.9% (44/58) versus 33.3% (10/30), χ²=15.084, P=0.000]. Furthermore, the positive rate of FXYD6 protein expression in the well and moderately differentiated hilar cholangiocar-cinoma tissue was significantly higher than that in the poorly differentiated hilar cholangiocarcinoma [85.4% (35/41) versus 52.9% (9/17), χ²=5.243, P=0.022], which was not related to the gender (χ²=0.000, P=1.000), age (χ²=1.248, P=0.264), T stage (χ²=0.466, P=0.495), lymph node metastasis (χ²=0.357, P=0.550), pathological stage (χ²=0.005, P=0.944), and perineural invasion (χ²=3.016, P=0.082). Conclustion The positive rate of FXYD6 protein expression is associated with differentiation of hilar cholangiocarcinoma, which might be a new biomarker of it.

Citation： CHENXiong-fei, ZHOUNing-xin, ZHANGHong-hong. Expression of FXYD6 in Hilar Cholangiocarcinoma Tissue and Its Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(11): 1344-1347. doi: 10.7507/1007-9424.20160344 Copy

1.	Miyashita T, Akiyama K, Inamoto R, et al. Presence of FXYD6 in the endolymphatic sac epithelia. Neurosci Lett, 2012, 513(1):47-50.
2.	窦春青, 岳鑫, 周宁新. hFXYD6反义核酸对胆管癌细胞体外增殖和侵袭能力的影响. 世界华人消化杂志, 2007, 15(10):929-935.
3.	刘军桂, 周宁新, 张效东. FXYD6 shRNA表达载体的构建及其在体外对胰腺癌细胞增殖的影响. 生物技术通迅, 2009, 20(4):458-461.
4.	Gao Q, Chen X, Duan H, et al. FXYD6:a novel therapeutic target toward hepatocellular carcinoma. Protein Cell, 2014, 5(7):532-543.
5.	Li ZM, Zhang HY, Wang YX, et al. MicroRNA-137 is downregulated in human osteosarcoma and regulates cell proliferation and migra-tion through targeting FXYD6. J Drug Target, 2016, 24(2):102-110.
6.	Hu HJ, Mao H, Shrestha A, et al. Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experi-ence in China. World J Gastroenterol, 2016, 22(8):2601-2610.
7.	Loftas P, Arbman G, Sun XF, et al. FXYD3 expression in relation to local recurrence of rectal cancer. Radiat Oncol J, 2016, 34(1):52-58.
8.	Ramírez-Backhaus M, Fernández-Serra A, Rubio-Briones J, et al. External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes. Actas Urol Esp, 2015, 39(8):473-481.
9.	Li Y, Zhang X, Xu S,et al. Expression and clinical significance of FXYD3 in endometrial cancer. Oncol Lett, 2014, 8(2):517-522.
10.	Raman P, Purwin T, Pestell R, et al. FXYD5 is a marker for poor prognosis and a potential driver for metastasis in ovarian carcinomas. Cancer Inform, 2015, 14:113-119.
11.	Liu CC, Teh R, Mozar CA, et al. Silencing overexpression of FXYD3 protein in breast cancer cells amplifies effects of doxorubicin and γ-radiation on Na(+)/K (+)-ATPase and cell survival. Breast Cancer Res Treat, 2016, 155(2):203-213.
12.	Giotakis I, Chrysovergis A, Georgolios A, et al. Adhesion molecules in cancer of the head and neck:role of dysadherin. J BUON, 2011, 16(4):609-612.
13.	Kadowaki K, Sugimoto K, Yamaguchi F, et al. Phosphohippolin expression in the rat central nervous system. Brain Res Mol Brain Res, 2004, 125(1-2):105-112.
14.	Biesemann C, Gronborg M, Luquet E, et al. Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting. EMBO J, 2014, 33(2):157-170.
15.	Shiina N, Yamaguchi K, Tokunaga M. RNG105 deficiency impairs the dendritic localilocalization of mRNAs for Na⁺/K⁺ ATPase subunit isoforms and leads to the degeneration of neuronal networks. J Neurosci, 2010, 30(38):12816-12830.
16.	肖梅, 周宁新, 高丽杰, 等. 半定量检测胆管癌组织中人fxyd6基因的表达. 中国普外基础与临床杂志, 2008, 15(2):83-87.
17.	Liu J, Zhou N, Zhang X. A monoclonal antibody against human FXYD6. Hybridoma (Larchmt), 2011, 30(5):487-490.
18.	李征, 何剪太. FXYD6蛋白在鼻咽癌组织中的表达. 中国耳鼻喉颅底外科杂志, 2011, 17(4):252-254, 258.
19.	Murakami Y, Uemura K, Sudo T, et al. Perineural invasion in extra-hepatic cholangiocarcinoma:prognostic impact and treatment stra-tegies. J Gastrointest Surg, 2013, 17(8):1429-1439.
20.	李成刚, 黄志强, 韦立新, 等. 肝门部胆管癌神经浸润及围肝门部神经丛的分布. 中华医学杂志, 2012, 92(38):2699-2702.
21.	Bibert S, Liu CC, Figtree GA, et al. FXYD proteins reverse inhibition of the Na+-K+ pump mediated by glutathionylation of its beta1 subunit. J Biol Chem, 2011, 286(21):18562-18572.
22.	Shindo Y, Morishita K, Kotake E, et al. FXYD6, a Na, K-ATPase regulator, is expressed in type Ⅱ taste cells. Biosci Biotechnol Biochem, 2011, 75(6):1061-1066.
23.	Tummala R, Wolle D, Barwe SP, et al. Expression of Na, K-ATPase-beta(1) subunit increases uptake and sensitizes carcinoma cells to oxaliplatin. Cancer Chemother Pharmacol, 2009, 64(6):1187-1194.

1. Miyashita T, Akiyama K, Inamoto R, et al. Presence of FXYD6 in the endolymphatic sac epithelia. Neurosci Lett, 2012, 513(1):47-50.
2. 窦春青, 岳鑫, 周宁新. hFXYD6反义核酸对胆管癌细胞体外增殖和侵袭能力的影响. 世界华人消化杂志, 2007, 15(10):929-935.
3. 刘军桂, 周宁新, 张效东. FXYD6 shRNA表达载体的构建及其在体外对胰腺癌细胞增殖的影响. 生物技术通迅, 2009, 20(4):458-461.
4. Gao Q, Chen X, Duan H, et al. FXYD6:a novel therapeutic target toward hepatocellular carcinoma. Protein Cell, 2014, 5(7):532-543.
5. Li ZM, Zhang HY, Wang YX, et al. MicroRNA-137 is downregulated in human osteosarcoma and regulates cell proliferation and migra-tion through targeting FXYD6. J Drug Target, 2016, 24(2):102-110.
6. Hu HJ, Mao H, Shrestha A, et al. Prognostic factors and long-term outcomes of hilar cholangiocarcinoma:A single-institution experi-ence in China. World J Gastroenterol, 2016, 22(8):2601-2610.
7. Loftas P, Arbman G, Sun XF, et al. FXYD3 expression in relation to local recurrence of rectal cancer. Radiat Oncol J, 2016, 34(1):52-58.
8. Ramírez-Backhaus M, Fernández-Serra A, Rubio-Briones J, et al. External validation of FXYD3 and KRT20 as predictive biomarkers for the presence of micrometastasis in muscle invasive bladder cancer lymph nodes. Actas Urol Esp, 2015, 39(8):473-481.
9. Li Y, Zhang X, Xu S,et al. Expression and clinical significance of FXYD3 in endometrial cancer. Oncol Lett, 2014, 8(2):517-522.
10. Raman P, Purwin T, Pestell R, et al. FXYD5 is a marker for poor prognosis and a potential driver for metastasis in ovarian carcinomas. Cancer Inform, 2015, 14:113-119.
11. Liu CC, Teh R, Mozar CA, et al. Silencing overexpression of FXYD3 protein in breast cancer cells amplifies effects of doxorubicin and γ-radiation on Na(+)/K (+)-ATPase and cell survival. Breast Cancer Res Treat, 2016, 155(2):203-213.
12. Giotakis I, Chrysovergis A, Georgolios A, et al. Adhesion molecules in cancer of the head and neck:role of dysadherin. J BUON, 2011, 16(4):609-612.
13. Kadowaki K, Sugimoto K, Yamaguchi F, et al. Phosphohippolin expression in the rat central nervous system. Brain Res Mol Brain Res, 2004, 125(1-2):105-112.
14. Biesemann C, Gronborg M, Luquet E, et al. Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting. EMBO J, 2014, 33(2):157-170.
15. Shiina N, Yamaguchi K, Tokunaga M. RNG105 deficiency impairs the dendritic localilocalization of mRNAs for Na⁺/K⁺ ATPase subunit isoforms and leads to the degeneration of neuronal networks. J Neurosci, 2010, 30(38):12816-12830.
16. 肖梅, 周宁新, 高丽杰, 等. 半定量检测胆管癌组织中人fxyd6基因的表达. 中国普外基础与临床杂志, 2008, 15(2):83-87.
17. Liu J, Zhou N, Zhang X. A monoclonal antibody against human FXYD6. Hybridoma (Larchmt), 2011, 30(5):487-490.
18. 李征, 何剪太. FXYD6蛋白在鼻咽癌组织中的表达. 中国耳鼻喉颅底外科杂志, 2011, 17(4):252-254, 258.
19. Murakami Y, Uemura K, Sudo T, et al. Perineural invasion in extra-hepatic cholangiocarcinoma:prognostic impact and treatment stra-tegies. J Gastrointest Surg, 2013, 17(8):1429-1439.
20. 李成刚, 黄志强, 韦立新, 等. 肝门部胆管癌神经浸润及围肝门部神经丛的分布. 中华医学杂志, 2012, 92(38):2699-2702.
21. Bibert S, Liu CC, Figtree GA, et al. FXYD proteins reverse inhibition of the Na+-K+ pump mediated by glutathionylation of its beta1 subunit. J Biol Chem, 2011, 286(21):18562-18572.
22. Shindo Y, Morishita K, Kotake E, et al. FXYD6, a Na, K-ATPase regulator, is expressed in type Ⅱ taste cells. Biosci Biotechnol Biochem, 2011, 75(6):1061-1066.
23. Tummala R, Wolle D, Barwe SP, et al. Expression of Na, K-ATPase-beta(1) subunit increases uptake and sensitizes carcinoma cells to oxaliplatin. Cancer Chemother Pharmacol, 2009, 64(6):1187-1194.

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Expression of FXYD6 in Hilar Cholangiocarcinoma Tissue and Its Clinical Significance

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