What question did this study set out to answer?

This research aims to explore the association between mucin RNA isoforms and clinical severity scores in ulcerative colitis patients.

January 23, 2026

P0069Mucin RNA Isoform Expression and Its Association with Clinical Severity Scores and Barrier Gene Networks in Ulcerative Colitis

Key Points

This research aims to explore the association between mucin RNA isoforms and clinical severity scores in ulcerative colitis patients.
RNA sequencing of colonic biopsies from ulcerative colitis patients and healthy controls
Correlation analysis using multinomial regression to assess associations between mucin isoforms and clinical scores
Evaluation of relationships between mucin expression and barrier-related genes
Increased expression of MUC1, MUC4, and MUC16 in patients with mild to moderate disease severity
MUC4 and MUC16 expression significantly associated with moderate and severe clinical scores
Strong correlations found between mucin isoforms and barrier-related genes like JAK2, STAT1, and STAT3

Abstract

Abstract Background Mucosal healing is a key therapeutic endpoint for ulcerative colitis (UC) patients and is defined as endoscopic improvement and histological remission without taking barrier healing into account. Mucins are critical components of the mucosal barrier that give rise to structurally diverse isoforms. Recently, we reported mucin mRNA isoforms capturing patient heterogeneity and barrier function1. We explored the relationship between clinical scoring systems (i.e. patient reported outcomes, PRO2; Ulcerative Colitis Endoscopic Index of Severity, UCEIS; Mayo Endoscopic Score, MES; Geboes scores) in UC patients and mucin mRNA isoforms, as well as their correlation with barrier-related genes. Methods RNA from colonic biopsies of UC patients (27 non-inflamed; 36 inflamed) and healthy controls (n = 35, iFOBT’s with negative colonoscopy), was sequenced. Reads were mapped to our mucin isoform landscape 1 using Kallisto and analysed with Sleuth. The PRO2, UCEIS, MES, and Geboes scores were categorised into four bins: no disease, mild, moderate, severe. Associations between scores and mucin RNA isoforms 1 were assessed using multinomial regression. The correlations with barrier-related genes were also assessed. Results When considering the PRO2 score, an increased expression of the MUC1 (ENST00000462317.5), MUC4 (PB.1238.363) and MUC16 (ENST00000397910.8) RNA isoforms was observed in UC patients with mild and moderate disease (Fig. 1). Expression of MUC16 (ENST00000397910.8) was increased in patients with mild to severe disease as defined by the MES scoring whereas an increased expression of MUC4 (PB.1238.363) and decreased expression of MUC5B (PB.2816.52) and MUC20 (PB.1239.830) significantly associated with moderate and severe scores (Fig. 1). Regarding the UCEIS scores, expression of MUC16 (ENST00000397910.8) was increased in UC patients with mild to moderate disease but decreased in patients with severe disease activity (Fig. 1). Altered expression levels of MUC4 (PB.1238.363), MUC5B (PB.2816.52) and MUC20 (PB.1239.830) associated with moderate Geboes scores. Correlation analysis (|r| ≥ 0.5, p 0.05) revealed strong associations between barrier-related genes and MUC1 (ENST00000462317.5), MUC20 (ENST00000447234.7), MUC4 (PB.1238.363), and MUC5AC (PB.2811.15), and to a lesser extent with MUC20 (PB.1239.830) and MUC5B (PB.2816.52) (Fig. 2). The above mentioned MUC1, MUC4, and MUC5AC isoform expressions positively correlated with JAK2 expression; the MUC4 isoform also with JAK1 and STAT3 and the MUC1 isoform with STAT1 and STAT3 (Fig. 2). Conclusion Distinct mucin RNA isoforms are associated with disease activity and key barrier-related genes (e.g. JAK/STAT pathways), further supporting their potential for monitoring mucosal healing. Reference: 1Arras, W., Breugelmans, T., Oosterlinck, B., De Man, J. G., Malhotra-Kumar, S., Abrams, S.,... & Smet, A. (2024). The intestinal mucin isoform landscape reveals region-specific biomarker panels for inflammatory bowel disease patient stratification. Journal of Crohn’s and Colitis, jjae155 Conflict of interest: Dr. Oosterlinck, Baptiste: Supported by the Antwerp University Valorisation funds (IOF-POC number: FFI230207) Gassman, Julie: Supported by the Antwerp University Valorisation funds (IOF-POC number: FFI230207) Jauregui-Amezaga, Aranzazu: I declare that I have no personal financial conflicts of interest related to my scientific activities. Any research funding received from Takeda, Johnson & Johnson, and AbbVie has been allocated to the research group to which I belong and has been used exclusively to support institutional or group-based research initiatives, with no personal financial benefit. Somers, Michael: None De Man, Joris: no conflicts De Winter, Benedicte: grants from the University of Antwerp and the FWO (Fund for scientific research in Flanders) Further no conflicts of interest Smet, Annemieke: Annemieke Smet is supported by an internal university fund of the Antwerp University (BOF-SEP FFB240386) and a national fund of the Research Foundation - Flanders (Belgium FWO OZ10337). Annemieke Smet is also inventor of patent applications related to mucin isoforms in diseases characterized by barrier dysfunction, including IBD, GI cancers and respiratory diseases (WO/2021/013479 WO2022/003061 EP23214719.9).

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