{"doi":"10.1093/ecco-jcc/jjaf026","title":"A transcriptomic score to classify the inflammation-dysplasia-cancer sequence lesions in inflammatory bowel disease","abstract":"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.","journal":"Journal of Crohn s and Colitis","year":2025,"id":533270,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9534,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1415164,"name":"Nicolas Rosewick","orcid":"0000-0002-4443-2492","position":1,"is_corresponding":false},{"id":1415502,"name":"Maxfield Kelsey","orcid":null,"position":2,"is_corresponding":false},{"id":644379,"name":"Eric Trépo","orcid":"0000-0003-0475-3934","position":3,"is_corresponding":false},{"id":1247462,"name":"Frédérick Libert","orcid":"0009-0004-1429-9936","position":4,"is_corresponding":false},{"id":1071468,"name":"Martine De Vos","orcid":"0000-0002-0496-7038","position":5,"is_corresponding":false},{"id":1415503,"name":"Filip Baert","orcid":null,"position":6,"is_corresponding":false},{"id":1415165,"name":"Tom G. Moreels","orcid":"0000-0002-4965-7324","position":7,"is_corresponding":false},{"id":697923,"name":"Édouard Louis","orcid":"0000-0002-1287-7075","position":8,"is_corresponding":false},{"id":1415504,"name":"Jean-François Rahier","orcid":null,"position":9,"is_corresponding":false},{"id":1120687,"name":"Pieter Demetter","orcid":"0000-0001-7981-4645","position":10,"is_corresponding":false},{"id":98109,"name":"John M. Sedivy","orcid":"0000-0001-9363-4253","position":11,"is_corresponding":false},{"id":629666,"name":"Séverine Vermeire","orcid":"0000-0001-9942-3019","position":12,"is_corresponding":false},{"id":807134,"name":"Denis Franchimont","orcid":"0000-0001-8856-3462","position":13,"is_corresponding":false},{"id":1415163,"name":"Anneline Cremer","orcid":"0000-0002-2531-268X","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:51:32.301795Z","pmid":"39945142","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}