A collaborative research effort between Baylor College of Medicine and Washington University School of Medicine has made significant progress in understanding Barrett’s esophagus. This condition affects the esophageal lining and can lead to esophageal adenocarcinoma, a serious cancer.
The study, published in the Journal of Clinical Investigation, highlights changes in two key genes, SOX2 and CDX2, which play roles in maintaining the identity of the esophagus and intestine. These alterations contribute to Barrett's esophagus development. The findings may help identify individuals at risk and offer strategies to prevent progression to cancer.
Dr. Ramon Jin from Washington University emphasized the severity of esophageal adenocarcinoma: “Esophageal adenocarcinoma is one of the fastest growing solid cancers. It is difficult to treat, and there are no effective screening techniques available.” He noted that patients often present with advanced disease.
Barrett’s esophagus typically arises after prolonged acid and bile reflux exposure, causing cells in the esophagus lining to resemble those found in the stomach or intestine. Dr. Jason Mills from Baylor explained: “The esophagus... adapts to acid reflux by becoming more like the stomach or the intestine.” However, eliminating reflux does not reverse Barrett’s changes.
Jin described how Barrett’s lesions exhibit abnormal cell proliferation: “Under the microscope, Barrett’s lesions show increased cell proliferation and a disorganized tissue.”
To explore cellular transformation drivers, researchers examined transcription factors SOX2 and CDX2. They created organoids from patient samples revealing that a shift towards less SOX2 and more CDX2 prompts cells away from their normal state.
In addition, a mouse model was developed where Sox2 could be deactivated selectively in the esophagus. This led to early-stage Barrett's characteristics similar to humans.
These insights suggest that altering SOX2 and CDX2 balance due to acid or bile exposure may trigger Barrett's transformation process. Such understanding could pave new avenues for early intervention strategies.
Contributors Yuanwei Xu, T. Mamie Lih, Yang-Zhe Huang among others participated in this study with affiliations including Baylor College of Medicine and Johns Hopkins University.
For details on financial support sources for this research, refer to the publication.
