Short noncoding RNAs as predictive biomarkers for the development from inflammatory bowel disease unclassified to Crohn’s disease or ulcerative colitis

Jaslin P. James*, Lene Buhl Riis, Rolf Søkilde, Mikkel Malham, Estrid Høgdall, Ebbe Langholz, Boye Schnack Nielsen

*Corresponding author af dette arbejde

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Abstract

Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn’s disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60–97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.
OriginalsprogEngelsk
Artikelnummere0297353
TidsskriftPLoS ONE
Vol/bind19
Udgave nummer2 February
Antal sider16
ISSN1932-6203
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Funding: This work was supported by Aage Louis Hansen fonden [J.nr.20-2B-5995]; Herlev internal research funding [after year, 2019]; Colitis-Crohn Foreningen [2021]; Torben og Alice Frimodts Fond [FK1900]; Aase and Ejnar Danielsen’s Foundation [20-10-0411] All the funding was received towards JPJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2024 James et al. This is an open access article distributed under the terms of the Creative Commons Attribution License,

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