Meta-Analysis of IBD Gut Samples Gene Expression Identifies Specific Markers of Ileal and Colonic Diseases.
IBD
disease location
meta-analysis
transcriptome
Journal
Inflammatory bowel diseases
ISSN: 1536-4844
Titre abrégé: Inflamm Bowel Dis
Pays: England
ID NLM: 9508162
Informations de publication
Date de publication:
04 05 2022
04 05 2022
Historique:
received:
02
08
2021
pubmed:
21
12
2021
medline:
10
5
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation and tissue damages in limited segments of the digestive tract. Pathogenesis in the tissue and mucosal inflammation probably differs according to disease location. Our aim was to further analyze transcriptomic profiles in different locations of IBD, differentiating ulcerative colitis (UC), colonic Crohn's disease (CD), ileal CD, and pouchitis, with respect to normal colonic and ileal mucosa. We thus performed a meta-analysis focusing on specific transcriptomic signatures of ileal and colonic diseases. We identified 5 cohorts with available transcriptomic data in ileal or colonic samples from active IBD and non-IBD control samples. The meta-analysis was performed on 1047 samples. In each cohort separately, we compared gene expression in CD ileitis and normal ileum; in CD colitis, UC, and normal colon; and finally in pouchitis and normal ileum. We identified specific markers of ileal (FOLH1, CA2) and colonic (REG3A) inflammation and showed that, with disease, some cells from the ileum start to express colonic markers. We confirmed by immunohistochemistry that these markers were specifically present in ileal or colonic diseases. We highlighted that, overall, colonic CD resembles UC and is distinct from ileal CD, which is in turn closer to pouchitis. We demonstrated that ileal and colonic diseases exhibit specific signatures, independent of their initial clinical classification. This supports molecular, rather than clinical, disease stratification, and may be used to design drugs specifically targeting ileal or colonic diseases. We perform a meta-analysis of publicly available inflammatory bowel disease transcriptomes and identify FOLH1, REG3A, and CA2 as specific markers of ileal and colonic diseases. We demonstrate that Crohn’s colitis resembles ulcerative colitis, while Crohn’s ileitis resembles pouchitis.
Sections du résumé
BACKGROUND
Inflammatory bowel diseases (IBDs) are characterized by chronic inflammation and tissue damages in limited segments of the digestive tract. Pathogenesis in the tissue and mucosal inflammation probably differs according to disease location. Our aim was to further analyze transcriptomic profiles in different locations of IBD, differentiating ulcerative colitis (UC), colonic Crohn's disease (CD), ileal CD, and pouchitis, with respect to normal colonic and ileal mucosa. We thus performed a meta-analysis focusing on specific transcriptomic signatures of ileal and colonic diseases.
METHODS
We identified 5 cohorts with available transcriptomic data in ileal or colonic samples from active IBD and non-IBD control samples. The meta-analysis was performed on 1047 samples. In each cohort separately, we compared gene expression in CD ileitis and normal ileum; in CD colitis, UC, and normal colon; and finally in pouchitis and normal ileum.
RESULTS
We identified specific markers of ileal (FOLH1, CA2) and colonic (REG3A) inflammation and showed that, with disease, some cells from the ileum start to express colonic markers. We confirmed by immunohistochemistry that these markers were specifically present in ileal or colonic diseases. We highlighted that, overall, colonic CD resembles UC and is distinct from ileal CD, which is in turn closer to pouchitis.
CONCLUSIONS
We demonstrated that ileal and colonic diseases exhibit specific signatures, independent of their initial clinical classification. This supports molecular, rather than clinical, disease stratification, and may be used to design drugs specifically targeting ileal or colonic diseases.
We perform a meta-analysis of publicly available inflammatory bowel disease transcriptomes and identify FOLH1, REG3A, and CA2 as specific markers of ileal and colonic diseases. We demonstrate that Crohn’s colitis resembles ulcerative colitis, while Crohn’s ileitis resembles pouchitis.
Autres résumés
Type: plain-language-summary
(eng)
We perform a meta-analysis of publicly available inflammatory bowel disease transcriptomes and identify FOLH1, REG3A, and CA2 as specific markers of ileal and colonic diseases. We demonstrate that Crohn’s colitis resembles ulcerative colitis, while Crohn’s ileitis resembles pouchitis.
Identifiants
pubmed: 34928348
pii: 6470736
doi: 10.1093/ibd/izab311
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
775-782Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.