Overexpression of ATPase Na+/K+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma
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I-Chen Wu1,2,*, Yu-Kuei Chen3,*, Chun-Chieh Wu4, Yu-Jen Cheng5, Wei-Chung Chen6, Huey-Jiun Ko1, Yu-Peng Liu7,8, Chee-Yin Chai4, Hung-Shun Lin9, Deng-Chyang Wu1,2, Ming-Tsang Wu7,10,11
1Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
2Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
3Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan
4Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
5Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan
6Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
7Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
8Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
9Department of Laboratory Medicine & Department of Research, Education & Training, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
10Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
11Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
*These authors have contributed equally to this work
Ming-Tsang Wu, email: [email protected]
Keywords: ATPase Na+/K+ transporting alpha 1 polypeptide, microarray-based screening, arecoline, F344, esophageal squamous cell carcinoma
Received: December 30, 2015 Accepted: October 14, 2016 Published: November 10, 2016
This study aims to identify new upregulated genes related to secretory or membranous proteins to help detect esophageal squamous cell carcinoma (ESCC). First, we performed microarray-based screening of esophageal tumors from both N-nitrosomethylbenzylamine- and arecoline-induced F344 rats and seventeen human ESCC specimens. Candidate genes were validated by quantitative PCR (qPCR) and immunohistochemical (IHC) staining of ESCC tissues. Among the paired cancer and adjacent normal tissues from 14 ESCC patients, 10 pairs (71.4%) had overexpression of ATP1A1 (ATPase Na+/K+ transporting alpha 1 polypeptide) by qPCR (P = 0.0052). ATP1A1 protein expression was re-confirmed by tissue arrays in 243 ESCC tissues and 126 adjacent normal tissues and by ELISA in 78 serum specimens of ESCC patients. ATP1A1 was 12.3 times (adjusted odds ratio=12.3, 95% CI = 7.2-21.0) more likely to be overexpressed in cancer tissues than in normal tissues. ATP1A1 expression was also correlated to tumor stage. Patients with higher serum ATP1A1 levels had a 2.9-fold (95% CI = 1.1-7.4) risk of late-stage disease (stages III-IV vs. I-II). Downregulation of ATP1A1 expression inhibited the migration and invasion ability of ESCC cell lines in vitro. We concluded that the overexpression of ATP1A1 is strongly associated with the presence and severity of ESCC.
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