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Barrett’s esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett’s malignant progression, using a meta-analysis approach on gene expression data. This  in silico  strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett’s progression,  CYR61  and  TAZ . Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that  CYR61  and  TAZ  have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett’s samples associated with high-grade dysplasia/adenocarcinoma. In our cohort  CYR61  and  TAZ  up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett’s esophagus index samples. Finally, we found that  CYR61  and  TAZ  over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both  CYR61  and  TAZ  genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett’s esophagus neoplastic progression.

CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progression