[en] BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is associated with a higher risk of developing colorectal cancer, according to the inflammation-dysplasia-cancer (IDC) sequence from inflammation to colitis-associated colorectal cancer (CAC). The objective of this study was to identify and generate a transcriptomic signature and score, related to the IDC sequence, that could ultimately classify dysplasia and cancer in IBD. METHODS: Demographics, clinical parameters, histological characteristics, and RNA-sequencing data were evaluated on 134 formalin-fixed paraffin-embedded lesions from 2 independent cohorts of IBD patients with low- or high-grade dysplasia (LGD, HGD) and/or CAC. An ordinal logistic regression screened for significant IDC sequence-associated genes that were computed in a transcriptomic signature score. RESULTS: Principal component analysis and unsupervised clustering on 1% of the most variable genes showed a good clustering between the 4 lesion groups (Normal Mucosa, Inflamed Mucosa, LGD/HGD, and CAC). A gene signature was identified on 27 genes that correlated with the lesion groups in the exploratory cohort. The most weighted gene in this transcriptomic signature was the long non-coding regulatory RNA KCNQ1OT1, a gatekeeper against genomic instability and transposon activation. Based on the expression of these 27 genes, we built and validated a transcriptomic signature score to classify dysplasia and CAC. The overall accuracy of the transcriptomic signature score was 85.71% in the exploratory cohort and 90.91% in the validation cohort. CONCLUSION: We identified a tissue-based transcriptomic score to classify IDC lesions in IBD patients and uncovered some of the pivotal genes in carcinogenesis related to inflammation in IBD.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Cremer, Anneline; Department of Gastroenterology, HUB Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. ; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Rosewick, Nicolas; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Kelsey, Maxfield; Center on the Biology of Aging, and the Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, United States.
Trépo, Eric; Department of Gastroenterology, HUB Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. ; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Libert, Frédérick; Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles, Brussels, Belgium.
De Vos, Martine; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.
Baert, Filip; Department of Gastroenterology, AZ Delta, Roeselare, Belgium.
Moreels, Tom; Department of Gastroenterology, University Hospital Antwerp, Edegem, Belgium.
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Rahier, Jean-François; Department of Gastroenterology, CHU UCL Namur site Mont-Godinne, Université Catholique de Louvain, Yvoir, Belgium.
Demetter, Pieter; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
Sedivy, John M; Center on the Biology of Aging, and the Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, United States.
Vermeire, Séverine ; Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium.
Franchimont, Denis; Department of Gastroenterology, HUB Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. ; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium.
A transcriptomic score to classify the inflammation-dysplasia-cancer sequence lesions in inflammatory bowel disease.
Publication date :
05 March 2025
Journal title :
Journal of Crohn's and Colitis
ISSN :
1873-9946
eISSN :
1876-4479
Publisher :
Oxford University Press, Oxford, Gb
Volume :
19
Issue :
3
Peer reviewed :
Peer Reviewed verified by ORBi
Funding number :
Research Foundation against Cancer-Belgium/; Erasme Foundation/; R01 AG016694/AG/NIA NIH HHS/United States; Televie/; P01 AG051449/NH/NIH HHS/United States
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