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Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn’s Disease

2022; Oxford University Press; Volume: 16; Issue: 8 Linguagem: Inglês

10.1093/ecco-jcc/jjac021

1876-4479

Marjolaine Ngollo, Kevin Pérez, Nassim Hammoudi, Yuri Gorelik, Marc Delord, Claire Auzolle, Hugo Bottois, Dominique Cazals–Hatem, Madeleine Bezault, Stéphane Nancey, Maria Nachury, Xavier Tréton, Mathurin Fuméry, Anthony Buisson, Nicolas Barnich, Philippe Seksik, Hélène Corte, Pierre Cattan, Mircea Chirica, Nicolas Munoz‐Bongrand, Jean-Marc Gornet, Clotilde Baudry, Nelson Lourenço, Marianne Maillet, My‐Linh Tran‐Minh, A Nisard, Joëlle Bonnet, Leïla Chedouba, Harry Sokol, Laurent Beaugerie, Anne Bourrier, Isabelle Nion–Larmurier, Philippe Marteau, Cécilia Landman, Sylvie Rajca, Elodie Quévrain, Loïc Brot, Najim Chafaı̈, Jéremie H. Lefèvre, Emmanuel Tiret, Magali Svrcek, Nadia Hoyau-Idrissi, Jean François Fléjou, Yoram Bouhnik, Carmen Stefănescu, Nathalie Guedj, Yves Panís, Léon Maggiori, Olivier Corcos, Gilles Bommelaer, Marion Goutte, Emilie Vazeille, Michael Rodrigues, Pierre Sauvanet, Pierre Desreumaux, Maria Nachury, Coralie Sommeville, Jean‐Louis Dupas, Franck Brazier, Denis Chatelain, Christophe Attencourt, Charles Sabbagh, Martine Leconte, Gilles Boschetti, Bernard Flourié, Yves François, Eddy Cotte, Anne-Laure Charlois, Peggy Falgon, Driffa Moussata, Marion Chauvenet, Sarah Boyer, Xavier Hébuterne, Jérôme Filippi, Paul Hofman, Madeleine Bezault, Shai S. Shen-Orr, Lionel Le Bourhis, Matthieu Allez,

Helicobacter pylori-related gastroenterology studies

Ileocolonic resection is frequently needed in the course of Crohn's disease [CD] treatment and post-operative recurrence is extremely common. Our main objective was to analyse gene expression in the mucosa of CD patients at the time of surgery and at post-operative endoscopy, in order to identify predictors and mechanisms of early endoscopic recurrence.We conducted transcriptome analyses on ileal mucosa samples collected from inflamed sections of the surgical specimens [n = 200], from ileal resection margins [n = 149] and in the neo-terminal ileum 6 months after surgery [n = 122]; these were compared with non-inflammatory bowel disease controls [n = 25]. The primary endpoint was post-operative endoscopic recurrence at 6 months. We applied regression models to identify gene signatures predicting endoscopic recurrence.Chronic inflammation was associated with strong expression of inflammatory genes [IL-6, IL-8, IL-1B] and decreased expression of genes involved in metabolic processes, but with a high inter-individual heterogeneity. Gene signatures associated with early endoscopic recurrence were mainly characterized by upregulation of TNFα, IFNγ, IL23A and IL17A. Pathway analyses showed that upregulation of mitochondrial dysfunction within the inflamed sections and JAK/STAT at the ileal margin were predictive of post-operative recurrence. A combined model integrating these top pathway signatures improved the prediction of endoscopic recurrence [area under the curve of 0.79]. STAT3 phosphorylation at the surgical ileal margin was associated with severe recurrence at 6 months.We identified several biological pathways in surgical ileal mucosa specimens associated with an increased risk of disease recurrence. Integration of the JAK/STAT and mitochondrial dysfunction pathways in the clinical model improved the prediction of post-operative recurrence.