Identification of gene expression profiles ...
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Article dans une revue scientifique: Article original
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Title :
Identification of gene expression profiles associated with an increased risk of post-operative recurrence in Crohn's disease.
Author(s) :
Ngollo, Marjolaine [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Perez, Kevin [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Hammoudi, Nassim [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Gorelik, Yuri [Auteur]
Technion - Israel Institute of Technology [Haifa]
Delord, Marc [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Auzolle, Claire [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Bottois, Hugo [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Cazals-Hatem, Dominique [Auteur]
Hôpital Beaujon [AP-HP]
Bezault, Madeleine [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Nancey, Stephane [Auteur]
Hospices Civils de Lyon [HCL]
Nachury, Maria [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Treton, Xavier [Auteur]
Hôpital Beaujon [AP-HP]
Fumery, Mathurin [Auteur]
CHU Amiens-Picardie
Buisson, Anthony [Auteur]
CHU Clermont-Ferrand
Barnich, Nicolas [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
Seksik, Philippe [Auteur]
CHU Saint-Antoine [AP-HP]
Shen-Orr, Sai S. [Auteur]
Technion - Israel Institute of Technology [Haifa]
Le Bourhis, Lionel [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Allez, Mathieu [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Perez, Kevin [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Hammoudi, Nassim [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Gorelik, Yuri [Auteur]
Technion - Israel Institute of Technology [Haifa]
Delord, Marc [Auteur]
Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH) [IRSL]
Auzolle, Claire [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Bottois, Hugo [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Cazals-Hatem, Dominique [Auteur]
Hôpital Beaujon [AP-HP]
Bezault, Madeleine [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Nancey, Stephane [Auteur]
Hospices Civils de Lyon [HCL]
Nachury, Maria [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Treton, Xavier [Auteur]
Hôpital Beaujon [AP-HP]
Fumery, Mathurin [Auteur]
CHU Amiens-Picardie
Buisson, Anthony [Auteur]
CHU Clermont-Ferrand
Barnich, Nicolas [Auteur]
Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte [M2iSH]
Seksik, Philippe [Auteur]
CHU Saint-Antoine [AP-HP]
Shen-Orr, Sai S. [Auteur]
Technion - Israel Institute of Technology [Haifa]
Le Bourhis, Lionel [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Allez, Mathieu [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Journal title :
Journal of Crohn's and Colitis
Abbreviated title :
J Crohns Colitis
Volume number :
16
Pages :
1269–1280
Publication date :
2022-02-13
ISSN :
1876-4479
English keyword(s) :
Crohn's disease
surgery
recurrence
prediction
transcriptome
surgery
recurrence
prediction
transcriptome
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Background and Aims
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 ...
Show more >Background and Aims 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. Methods 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. Results 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. Conclusion 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.Show less >
Show more >Background and Aims 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. Methods 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. Results 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. Conclusion 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.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-01-12T02:17:19Z
2024-03-04T09:28:38Z
2024-03-04T09:28:38Z