Overexpression of ATPase Na+/K+ 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.