Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis

Abstract

OBJECTIVES:Obesity is linked to increased mortality from many cancer types, and esophageal adenocarcinoma (EAC) displays one of the strongest epidemiological associations. The aims of this study are to dissect molecular pathways linking obesity with EAC and to determine if obesity is linked to increased aggressiveness of this disease.METHODS:Affymetrix microarrays identified altered signaling pathways in an EAC cell line following coculture with visceral adipose tissue or isolated adipocytes from viscerally obese EAC patients (n=6). Differentially expressed genes were subsequently investigated in patient tumor biopsies by quantitative reverse transcriptase PCR and examined with respect to obesity status, tumor biology, and patient survival.RESULTS:Visceral adipose tissue induced expression of genes involved in epithelial mesenchymal transition (EMT), plasminogen activator inhibitor (PAI)-1, and transcription factor SNAI2, in an EAC cell line. In EAC patient tumor biopsies from obese patients, we noted elevated expression of these genes, together with reduced expression of epithelial marker E-cadherin. SNAI2 was associated with EAC prognosis.CONCLUSIONS:Expression of EMT genes, PAI-1 and SNAI2, was elevated in tumors of obese EAC patients, and SNAI2 was associated with poor survival. Genes deregulated in obesity and associated with prognosis may represent potential targets for treatment stratification of obese EAC patients.