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

Maximilien Barret, Ludivine Doridot, Morgane Le Gall, Frédéric Beuvon, Sébastien Jacques, Anna Pellat, Arthur Belle, Einas Abou Ali, Marion Dhooge, Sarah Leblanc, Marine Camus, Carole Nicco, Romain Coriat, Stanislas Chaussade, Frédéric Batteux, Frédéric Prat
Author Information
  1. Maximilien Barret: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  2. Ludivine Doridot: Université de Paris, France.
  3. Morgane Le Gall: 3P5 Proteom'IC facility, Université de Paris, Institut Cochin, INSERM, CNRS, F-75014, France.
  4. Frédéric Beuvon: Genom'ic CNRS UMR8104, Paris, France.
  5. Sébastien Jacques: Université de Paris, France.
  6. Anna Pellat: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  7. Arthur Belle: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  8. Einas Abou Ali: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  9. Marion Dhooge: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  10. Sarah Leblanc: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  11. Marine Camus: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  12. Carole Nicco: Université de Paris, France.
  13. Romain Coriat: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  14. Stanislas Chaussade: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.
  15. Frédéric Batteux: Université de Paris, France.
  16. Frédéric Prat: Department of Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, France.

Abstract

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. 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 on Days 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. 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 (IL)-1 group (Z score = 2.159,  = 0.0137), while interferon-gamma (INFγ) and NUPR1 were inhibited (Z score = -2.375,  = 0.0022 and Z score = -2.333,  = 0.00131) in the stricture group. None of the activated or inhibited transcripts were still significantly so in any of the groups on Day 90. Our data suggest that IL-1 inhibition or INFγ supplementation could constitute promising targets for post-endoscopic esophageal stricture prevention.

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Word Cloud

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