Novel Biomarkers and Distinct Transcriptomic Profile of Barrett's Esophagus Epithelial Stem Cells

Abstract

Barretts esophagus, a metaplastic condition that originates in the distal esophagus, is the only known precursor lesion for the development of esophageal adenocarcinoma, which has a devasting 5-year survival rate of <20%. The large number of subjects diagnosed with Barretts esophagus, and therefore at higher risk for esophageal adenocarcinoma, underscores the necessity for biomarkers that would benefit surveillance and potentially early treatment. To address this, we generated epithelial stem cell organoids from normal gastric cardia, non-dysplastic and dysplastic Barretts esophagus, and esophageal and gastric adenocarcinoma. Interestingly, non-dysplastic and dysplastic Barretts esophagus displayed higher expression of multiple archetypical cancer-associated genes compared with both esophageal and gastric adenocarcinoma in addition to expression of the novel biomarker CT83. ST6GAL1, a Golgi sialyltransferase upregulated in multiple epithelioid cancers, was strongly upregulated in dysplastic Barretts esophagus at both mRNA and protein levels. ST6GAL1 protein also was highly expressed in esophageal adenocarcinoma, suggesting that regulation of ST6GAL1 may play a role in Barretts esophagus progression to esophageal adenocarcinoma and serve as a potential biomarker of the development of esophageal cancer.