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

Marjolaine Ngollo; Kevin Perez; Nassim Hammoudi; Yuri Gorelik; Marc Delord; Claire Auzolle; Hugo Bottois; Dominique Cazals-Hatem; Madeleine Bezault; Stephane Nancey; Maria Nachury; Xavier Treton; Mathurin Fumery; Anthony Buisson; Nicolas Barnich; Philippe Seksik; Helène Corte; Pierre Cattan; Mircea Chirica; Nicolas Munoz-Bongrand; Jean Marc Gornet; Clotilde Baudry; Nelson Lourenco; Marianne Maillet; My Linh Tran-Minh; Andree Nisard; Joelle Bonnet; Leila Chedouba; Harry Sokol; Laurent Beaugerie; Anne Bourrier; Isabelle Nion-Larmurier; Philippe Marteau; Cecilia Landman; Sylvie Rajca; Elodie Quevrain; Loic Brot; Najim Chafai; Jeremie H. Lefevre; Emmanuel Tiret; Magali Svrcek; Nadia Hoyau-Idrissi; Jean François Flejou; Yoram Bouhnik; Carmen Stefanescu; Nathalie Guedj; Yves Panis; Leon 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 Flourie; Yves François; Eddy Cotte; Anne Laure Charlois; Peggy Falgon; Driffa Moussata; Marion Chauvenet; Sarah Boyer; Xavier Hebuterne; Jerome Filippi; Paul Hofman; Madeleine Bezault; Shai S. Shen-Orr; Lionel Le Bourhis; Matthieu Allez

doi:https://doi.org/10.1093/ecco-jcc/jjac021

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

Marjolaine Ngollo, Kevin Perez, Nassim Hammoudi, Yuri Gorelik, Marc Delord, Claire Auzolle, Hugo Bottois, Dominique Cazals-Hatem, Madeleine Bezault, Stephane Nancey, Maria Nachury, Xavier Treton, Mathurin Fumery, Anthony Buisson, Nicolas Barnich, Philippe Seksik, Helène Corte, Pierre Cattan, Mircea Chirica, Nicolas Munoz-BongrandJean Marc Gornet, Clotilde Baudry, Nelson Lourenco, Marianne Maillet, My Linh Tran-Minh, Andree Nisard, Joelle Bonnet, Leila Chedouba, Harry Sokol, Laurent Beaugerie, Anne Bourrier, Isabelle Nion-Larmurier, Philippe Marteau, Cecilia Landman, Sylvie Rajca, Elodie Quevrain, Loic Brot, Najim Chafai, Jeremie H. Lefevre, Emmanuel Tiret, Magali Svrcek, Nadia Hoyau-Idrissi, Jean François Flejou, Yoram Bouhnik, Carmen Stefanescu, Nathalie Guedj, Yves Panis, Leon 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 Flourie, Yves François, Eddy Cotte, Anne Laure Charlois, Peggy Falgon, Driffa Moussata, Marion Chauvenet, Sarah Boyer, Xavier Hebuterne, Jerome Filippi, Paul Hofman, Madeleine Bezault, Shai S. Shen-Orr, Lionel Le Bourhis, Matthieu Allez

Medicine

Technion - Israel Institute of Technology

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1269-1280
Number of pages	12
Journal	Journal of Crohn's and Colitis
Volume	16
Issue number	8
DOIs	https://doi.org/10.1093/ecco-jcc/jjac021
State	Published - 1 Aug 2022

Keywords

Anastomosis, Surgical
Crohn Disease/drug therapy
Crohn's disease
Crohn’s disease
Endoscopy, Gastrointestinal
Humans
Ileum/surgery
Recurrence
Transcriptome
prediction
recurrence
surgery
transcriptome

All Science Journal Classification (ASJC) codes

Gastroenterology

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https://doi.org/10.1093/ecco-jcc/jjac021

Cite this

Ngollo, M., Perez, K., Hammoudi, N., Gorelik, Y., Delord, M., Auzolle, C., Bottois, H., Cazals-Hatem, D., Bezault, M., Nancey, S., Nachury, M., Treton, X., Fumery, M., Buisson, A., Barnich, N., Seksik, P., Corte, H., Cattan, P., Chirica, M., ... Allez, M. (2022). Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease. Journal of Crohn's and Colitis, 16(8), 1269-1280. https://doi.org/10.1093/ecco-jcc/jjac021

@article{4e3e34f4dd6f4ac8a4dac255adc78628,

title = "Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease",

abstract = "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.",

keywords = "Anastomosis, Surgical, Crohn Disease/drug therapy, Crohn's disease, Crohn{\textquoteright}s disease, Endoscopy, Gastrointestinal, Humans, Ileum/surgery, Recurrence, Transcriptome, prediction, recurrence, surgery, transcriptome",

author = "Marjolaine Ngollo and Kevin Perez and Nassim Hammoudi and Yuri Gorelik and Marc Delord and Claire Auzolle and Hugo Bottois and Dominique Cazals-Hatem and Madeleine Bezault and Stephane Nancey and Maria Nachury and Xavier Treton and Mathurin Fumery and Anthony Buisson and Nicolas Barnich and Philippe Seksik and Hel{\`e}ne Corte and Pierre Cattan and Mircea Chirica and Nicolas Munoz-Bongrand and Gornet, {Jean Marc} and Clotilde Baudry and Nelson Lourenco and Marianne Maillet and Tran-Minh, {My Linh} and Andree Nisard and Joelle Bonnet and Leila Chedouba and Harry Sokol and Laurent Beaugerie and Anne Bourrier and Isabelle Nion-Larmurier and Philippe Marteau and Cecilia Landman and Sylvie Rajca and Elodie Quevrain and Loic Brot and Najim Chafai and Lefevre, {Jeremie H.} and Emmanuel Tiret and Magali Svrcek and Nadia Hoyau-Idrissi and {Fran{\c c}ois Flejou}, Jean and Yoram Bouhnik and Carmen Stefanescu and Nathalie Guedj and Yves Panis and Leon Maggiori and Olivier Corcos and Gilles Bommelaer and Marion Goutte and Emilie Vazeille and Michael Rodrigues and Pierre Sauvanet and Pierre Desreumaux and Maria Nachury and Coralie Sommeville and Dupas, {Jean Louis} and Franck Brazier and Denis Chatelain and Christophe Attencourt and Charles Sabbagh and Martine Leconte and Gilles Boschetti and Bernard Flourie and Yves Fran{\c c}ois and Eddy Cotte and Charlois, {Anne Laure} and Peggy Falgon and Driffa Moussata and Marion Chauvenet and Sarah Boyer and Xavier Hebuterne and Jerome Filippi and Paul Hofman and Madeleine Bezault and Shen-Orr, {Shai S.} and {Le Bourhis}, Lionel and Matthieu Allez",

note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn{\textquoteright}s and Colitis Organisation. All rights reserved. For permissions, please email: [email protected].",

year = "2022",

month = aug,

day = "1",

doi = "https://doi.org/10.1093/ecco-jcc/jjac021",

language = "الإنجليزيّة",

volume = "16",

pages = "1269--1280",

journal = "Journal of Crohn's and Colitis",

issn = "1873-9946",

publisher = "Oxford University Press",

number = "8",

}

Ngollo, M, Perez, K, Hammoudi, N, Gorelik, Y, Delord, M, Auzolle, C, Bottois, H, Cazals-Hatem, D, Bezault, M, Nancey, S, Nachury, M, Treton, X, Fumery, M, Buisson, A, Barnich, N, Seksik, P, Corte, H, Cattan, P, Chirica, M, Munoz-Bongrand, N, Gornet, JM, Baudry, C, Lourenco, N, Maillet, M, Tran-Minh, ML, Nisard, A, Bonnet, J, Chedouba, L, Sokol, H, Beaugerie, L, Bourrier, A, Nion-Larmurier, I, Marteau, P, Landman, C, Rajca, S, Quevrain, E, Brot, L, Chafai, N, Lefevre, JH, Tiret, E, Svrcek, M, Hoyau-Idrissi, N, François Flejou, J, Bouhnik, Y, Stefanescu, C, Guedj, N, Panis, Y, Maggiori, L, Corcos, O, Bommelaer, G, Goutte, M, Vazeille, E, Rodrigues, M, Sauvanet, P, Desreumaux, P, Nachury, M, Sommeville, C, Dupas, JL, Brazier, F, Chatelain, D, Attencourt, C, Sabbagh, C, Leconte, M, Boschetti, G, Flourie, B, François, Y, Cotte, E, Charlois, AL, Falgon, P, Moussata, D, Chauvenet, M, Boyer, S, Hebuterne, X, Filippi, J, Hofman, P, Bezault, M, Shen-Orr, SS, Le Bourhis, L & Allez, M 2022, 'Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease', Journal of Crohn's and Colitis, vol. 16, no. 8, pp. 1269-1280. https://doi.org/10.1093/ecco-jcc/jjac021

TY - JOUR

T1 - Identification of Gene Expression Profiles Associated with an Increased Risk of Post-Operative Recurrence in Crohn's Disease

AU - Ngollo, Marjolaine

AU - Perez, Kevin

AU - Hammoudi, Nassim

AU - Gorelik, Yuri

AU - Delord, Marc

AU - Auzolle, Claire

AU - Bottois, Hugo

AU - Cazals-Hatem, Dominique

AU - Bezault, Madeleine

AU - Nancey, Stephane

AU - Nachury, Maria

AU - Treton, Xavier

AU - Fumery, Mathurin

AU - Buisson, Anthony

AU - Barnich, Nicolas

AU - Seksik, Philippe

AU - Corte, Helène

AU - Cattan, Pierre

AU - Chirica, Mircea

AU - Munoz-Bongrand, Nicolas

AU - Gornet, Jean Marc

AU - Baudry, Clotilde

AU - Lourenco, Nelson

AU - Maillet, Marianne

AU - Tran-Minh, My Linh

AU - Nisard, Andree

AU - Bonnet, Joelle

AU - Chedouba, Leila

AU - Sokol, Harry

AU - Beaugerie, Laurent

AU - Bourrier, Anne

AU - Nion-Larmurier, Isabelle

AU - Marteau, Philippe

AU - Landman, Cecilia

AU - Rajca, Sylvie

AU - Quevrain, Elodie

AU - Brot, Loic

AU - Chafai, Najim

AU - Lefevre, Jeremie H.

AU - Tiret, Emmanuel

AU - Svrcek, Magali

AU - Hoyau-Idrissi, Nadia

AU - François Flejou, Jean

AU - Bouhnik, Yoram

AU - Stefanescu, Carmen

AU - Guedj, Nathalie

AU - Panis, Yves

AU - Maggiori, Leon

AU - Corcos, Olivier

AU - Bommelaer, Gilles

AU - Goutte, Marion

AU - Vazeille, Emilie

AU - Rodrigues, Michael

AU - Sauvanet, Pierre

AU - Desreumaux, Pierre

AU - Nachury, Maria

AU - Sommeville, Coralie

AU - Dupas, Jean Louis

AU - Brazier, Franck

AU - Chatelain, Denis

AU - Attencourt, Christophe

AU - Sabbagh, Charles

AU - Leconte, Martine

AU - Boschetti, Gilles

AU - Flourie, Bernard

AU - François, Yves

AU - Cotte, Eddy

AU - Charlois, Anne Laure

AU - Falgon, Peggy

AU - Moussata, Driffa

AU - Chauvenet, Marion

AU - Boyer, Sarah

AU - Hebuterne, Xavier

AU - Filippi, Jerome

AU - Hofman, Paul

AU - Bezault, Madeleine

AU - Shen-Orr, Shai S.

AU - Le Bourhis, Lionel

AU - Allez, Matthieu

PY - 2022/8/1

Y1 - 2022/8/1

N2 - 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.

AB - 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.

KW - Anastomosis, Surgical

KW - Crohn Disease/drug therapy

KW - Crohn's disease

KW - Crohn’s disease

KW - Endoscopy, Gastrointestinal

KW - Humans

KW - Ileum/surgery

KW - Recurrence

KW - Transcriptome

KW - prediction

KW - recurrence

KW - surgery

KW - transcriptome

UR - http://www.scopus.com/inward/record.url?scp=85135853884&partnerID=8YFLogxK

U2 - https://doi.org/10.1093/ecco-jcc/jjac021

DO - https://doi.org/10.1093/ecco-jcc/jjac021

M3 - مقالة

C2 - 35143619

SN - 1873-9946

VL - 16

SP - 1269

EP - 1280

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

IS - 8

ER -

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

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