Pepsinogen/Proton Pump Co-Expression in Barrett's Esophageal Cells Induces Cancer-Associated Changes

Area of Science:

• Gastroenterology and Oncology
• Molecular Biology
• Cancer Research

Background:

• Barrett's esophagus (BE) is a risk factor for esophageal adenocarcinoma (EAC).
• Pepsin and gastric proton pump expression are found in some BE cases.
• The role of local pepsin and proton pump expression in BE carcinogenesis is not fully understood.

Purpose of the Study:

• To investigate the carcinogenic potential of pepsin and proton pump expression in BE.
• To examine global transcriptomic changes in a BE cell line with ectopic pepsinogen and/or proton pump expression.
• To identify molecular pathways affected by pepsin and proton pump expression in BE.

Main Methods:

• Utilized RNA sequencing to analyze transcriptomic changes.
• Employed a human BE cell line (BAR-T) engineered to express pepsinogen and/or gastric proton pump subunits.
• Compared gene expression profiles between engineered and parental cell lines.

Main Results:

• Differential gene expression was observed in pathways related to the tumor microenvironment and epithelial-mesenchymal transition.
• Key upstream regulators identified include TGFB1, ERBB2, p300-CBP, I-BET-151, and CD93.
• Cancer was the top associated disease for both coding and noncoding transcripts.

Conclusions:

• Data support the carcinogenic potential of pepsin and proton pump expression in BE.
• Identified molecular pathways affected by pepsin and proton pump expression warrant further investigation.
• Further research is needed to explore the role of these pathways in BE-associated carcinogenesis.