Mechanisms of esophageal stricture after extensive endoscopic resection: a transcriptomic analysis

Abstract

Introduction: Esophageal stricture is the most frequent adverse event after endoscopic resection for early esophageal neoplasia. Currently available treatments for the prevention of esophageal stricture are poorly effective and associated with major adverse events. Our aim was to identify transcripts specifically overexpressed or repressed in patients who have developed a post endoscopic esophageal stricture, as potential targets for stricture prevention. Patients and methods: We conducted a prospective single-center study in a tertiary endoscopy center. Patients scheduled for an endoscopic resection and considered at risk of esophageal stricture were offered inclusion in the study. The healthy mucosa and resection bed were biopsied at day 0, 14 and 90. A transcriptomic analysis by microarray was performed, and the differences in transcriptomic profile compared between patients with and without esophageal strictures. Results: Eight patients, four with esophageal stricture and four without, were analyzed. The mean ±SD circumferential extension of the mucosal defect was 85±11%. The transcriptomic analysis in the resection bed at day 14 found an activation of the Interleukin-1 group (Z score = 2.159, p = 0.0137), while Interferon γ and NUPR1 were inhibited (Z score = -2.375, p = 0.0022 and Z score =-2.333, p = 0.00131) in the stricture group. None of the activated or inhibited transcripts were still significantly so in any of the groups at day 90. Conclusions: Our data suggest that Interleukin-1 inhibition or Interferon-γ supplementation could constitute promising targets for post-endoscopic esophageal stricture prevention.