The transcriptomic analysis of low pH and bile acid induced gene expression in oesophageal cells

Abstract

Oesophageal adenocarcinoma (OAC) commonly arises from the presence of a premalignant lesion known as Barrett’s Oesophagus (BO). Gastro-oesophageal reflux disease (GORD) has been identified in epidemiological studies as a major risk factor in the pathogenesis of oesophageal adenocarcinoma. The major constituents of the refluxate in GORD and BO are gastric acid and bile acids such as deoxycholate (DCA). However, the impact of low pH and bile acids on gene expression has not been extensively studied in oesophageal cells. Global changes in gene and cytokine expression in response to these putative oesophageal carcinogens was examined. A transcriptomic method in conjunction with novel promoter bioinformatics was employed to assess gene induction in response to low pH and DCA exposure. The findings of this thesis provide further understanding of the role of low pH and DCA in the development and progression of OAC through the activation of cell specific transcriptional and inflammatory responses.