Overexpression of ATPase Na+/+ transporting alpha 1 polypeptide, ATP1A1, correlates with clinical diagnosis and progression of esophageal squamous cell carcinoma

Autor: Yu-Jen Cheng, Yu-Kuei Chen, Wei-Chung Chen, Huey-Jiun Ko, Hung-Shun Lin, Chee-Yin Chai, Ming-Tsang Wu, Yu-Peng Liu, Deng-Chyang Wu, Chun-Chieh Wu, I-Chen Wu
Rok vydání: 2015
Předmět:
0301 basic medicine
Oncology
Male
medicine.medical_specialty
Pathology
Esophageal Neoplasms
Carcinogenesis
F344
Arecoline
F344 rats
Esophageal squamous cell carcinoma
Dimethylnitrosamine
ATPase Na+/K+ transporting alpha 1 polypeptide
microarray-based screening
03 medical and health sciences
0302 clinical medicine
Esophageal tumors
Internal medicine
Cell Line
Tumor
Biomarkers
Tumor
Medicine
Animals
Humans
business.industry
Odds ratio
University hospital
Microarray Analysis
digestive system diseases
Rats
Up-Regulation
esophageal squamous cell carcinoma
Gene Expression Regulation
Neoplastic
Disease Models
Animal
030104 developmental biology
030220 oncology & carcinogenesis
Clinical diagnosis
Carcinoma
Squamous Cell
Disease Progression
Immunohistochemistry
Tissue Arrays
Sodium-Potassium-Exchanging ATPase
business
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // I-Chen Wu 1, 2, * , Yu-Kuei Chen 3, * , Chun-Chieh Wu 4 , Yu-Jen Cheng 5 , Wei-Chung Chen 6 , Huey-Jiun Ko 1 , Yu-Peng Liu 7, 8 , Chee-Yin Chai 4 , Hung-Shun Lin 9 , Deng-Chyang Wu 1, 2 , Ming-Tsang Wu 7, 10, 11 1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 2 Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan 4 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 5 Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan 6 Ph.D. Program in Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 7 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 8 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 9 Department of Laboratory Medicine & Department of Research, Education & Training, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 10 Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 11 Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan * These authors have contributed equally to this work Correspondence to: Ming-Tsang Wu, email: 960021@ms.kmuh.org.tw 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 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.
Databáze: OpenAIRE
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