title: Overexpression of ATPase Na+/+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Wu
authors.affiliation: Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan.
authors.forename: Yu-Kuei
authors.initials: YK
authors.lastname: Chen
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Huey-Jiun
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Department of Laboratory Medicine & Department of Research, Education & Training, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hung-Shun
authors.initials: HS
authors.lastname: Lin
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Tsang
authors.initials: MT
authors.lastname: Wu
mesh_terms: D000818:Animals; D001115:Arecoline / Q000633:toxicity; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000175:diagnosis*; D045744:Cell Line, Tumor; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D001115:Arecoline; C014707:nitrosobenzylmethylamine; C499076:ATP1A1 protein, human; D000254:Sodium-Potassium-Exchanging ATPase; D004128:Dimethylnitrosamine
keywords: ATPase Na+/K+ transporting alpha 1 polypeptide; F344; arecoline; esophageal squamous cell carcinoma; microarray-based screening