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Mucosal Gene Transcript Signatures in Treatment Naïve Inflammatory Bowel Disease: A Comparative Analysis of Disease to Symptomatic and Healthy Controls in the European IBD-Character Cohort
Department of Clinical Molecular Biology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
Health Services Research Unit (HØKH), Akershus University Hospital, Lørenskog, Norway; Department of Methods Development and Analytics, Division of Infectious Disease Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
Department of Clinical Molecular Biology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Methods Development and Analytics, Division of Infectious Disease Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway; Section for Clinical Molecular Biology (EpiGen), Akershus University Hospital, Lørenskog, Norway.
Department of Clinical Molecular Biology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
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2022 (English)In: Clinical and Experimental Gastroenterology, E-ISSN 1178-7023, Vol. 15, p. 5-25Article in journal (Refereed) Published
Abstract [en]

Background: Studies of the mucosal transcriptomic landscape have given new insight into the pathogenesis of inflammatory bowel disease (IBD). Recently, the predictive biomarker potential of gene expression signatures has been explored. To further investigate the mucosal gene expression in IBD, we recruited a cohort of treatment naïve patients and compared them to both symptomatic and healthy controls.

Methods: Altogether, 323 subjects were included: Crohn's disease (N = 75), ulcerative colitis (N = 87) and IBD unclassified (N = 3). Additionally, there were two control groups: symptomatic controls (N = 131) and healthy controls (N = 27). Mucosal biopsies were collected during ileocolonoscopy and gene expression in inflamed and non-inflamed mucosa was explored. Gene expression profiling was performed using Agilent G3 Human Gene Expression 860K v3 One-Color microarray. We recorded information about treatment escalation to anti-TNF agents or surgery, and anti-TNF response, to explore predictive opportunities of the mucosal transcriptome.

Results: Gene expression profiles in symptomatic controls in whom IBD had been excluded resembled that of IBD patients and diverged from that of healthy controls. In non-inflamed Crohn's disease and ulcerative colitis, gene set enrichment analysis revealed dysregulation of pathways involved in basic cellular biological processes. Mitochondria-associated pathways were dysregulated both in non-inflamed and inflamed Crohn's disease and ulcerative colitis (>2.6 normalized enrichment scores <-1.8). Gene expression signatures of Crohn's disease and ulcerative colitis did not predict time for treatment escalation (p = 0.175). No significant association was found between gene expression signatures and anti-TNF response.

Conclusion: Non-inflamed samples are probably superior to inflamed samples when exploring gene expression signatures in IBD and might reveal underlying mechanisms central for disease initiation. The gene expression signatures of the control groups were related to if they were symptomatic or not, which may have important implications for future study designs.

Place, publisher, year, edition, pages
Dove Medical Press Ltd. , 2022. Vol. 15, p. 5-25
Keywords [en]
Crohn’s disease, healthy controls, mitochondria, mucosal transcriptome, non-inflamed, prediction, symptomatic controls, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-97627DOI: 10.2147/CEG.S343468ISI: 000760064500001PubMedID: 35185343Scopus ID: 2-s2.0-85125093013OAI: oai:DiVA.org:oru-97627DiVA, id: diva2:1639618
Note

Funding agencies:

EU FP7 grant: IBD-CHARACTER 2858546

South-Eastern Norway Regional Health Authority 2014011 2018001

Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2024-01-09Bibliographically approved

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Bergemalm, DanielHalfvarson, Jonas

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