Journal of Crohn's & colitis · 2025
The Intestinal Mucin Isoform Landscape Reveals Region-Specific Biomarker Panels for Inflammatory Bowel Disease Patient Stratification.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Arras Wout, Breugelmans Tom, Oosterlinck Baptiste, De Man Joris G, Malhotra-Kumar Surbhi, Abrams Steven, Van Laere Steven, Macken Elisabeth, Somers Michaël, Jauregui-Amezaga Aranzazu, De Winter Benedicte Y, Smet Annemieke
Аннотация
BACKGROUND AND AIMS: Mucosal healing is considered a key therapeutic endpoint in inflammatory bowel diseases (IBD) and comprises endoscopic improvement of inflammation without taking barrier healing into account. Mucins are critical components of the mucosal barrier function that give rise to structurally diverse isoforms. Unraveling disease-associated mucin isoforms that could act as an indication for barrier function would greatly enhance IBD management.
METHODS: We present the intestinal mucin RNA isoform landscape in IBD and control patients using a targeted mucin isoform sequencing approach on a discovery cohort (n = 106). Random Forest modeling (n = 1683 samples) with external validation (n = 130 samples) identified unique mucin RNA isoform panels that accurately stratified IBD patients in multiple subpopulations based on inflammation, IBD subtype (Crohn's disease [CD], ulcerative colitis [UC]), and anatomical location of the intestinal tract (i.e. ileum, proximal colon, distal colon, and rectum).
RESULTS: Particularly, the mucin RNA isoform panels obtained from the inflamed UC and CD distal colon showed high performance in distinguishing inflamed biopsies from their control counterparts (AUC of 93.3% and 91.1% in the training, 95.0% and 96.0% in the test, and 89.5% and 78.3% in the external validation datasets, respectively). Furthermore, the differentially expressed MUC4 (PB.1238.363), MUC5AC (PB.2811.15), MUC16 (ENST00000397910.8), and MUC1 (ENST00000462317.5 and ENST00000620103.4) RNA isoforms frequently occurred throughout the different panels highlighting their role in IBD pathogenesis.
CONCLUSIONS: We unveiled region-specific mucin RNA isoform panels capturing the heterogeneity of the IBD patient population and showing great potential to indicate barrier function in IBD patients.
METHODS: We present the intestinal mucin RNA isoform landscape in IBD and control patients using a targeted mucin isoform sequencing approach on a discovery cohort (n = 106). Random Forest modeling (n = 1683 samples) with external validation (n = 130 samples) identified unique mucin RNA isoform panels that accurately stratified IBD patients in multiple subpopulations based on inflammation, IBD subtype (Crohn's disease [CD], ulcerative colitis [UC]), and anatomical location of the intestinal tract (i.e. ileum, proximal colon, distal colon, and rectum).
RESULTS: Particularly, the mucin RNA isoform panels obtained from the inflamed UC and CD distal colon showed high performance in distinguishing inflamed biopsies from their control counterparts (AUC of 93.3% and 91.1% in the training, 95.0% and 96.0% in the test, and 89.5% and 78.3% in the external validation datasets, respectively). Furthermore, the differentially expressed MUC4 (PB.1238.363), MUC5AC (PB.2811.15), MUC16 (ENST00000397910.8), and MUC1 (ENST00000462317.5 and ENST00000620103.4) RNA isoforms frequently occurred throughout the different panels highlighting their role in IBD pathogenesis.
CONCLUSIONS: We unveiled region-specific mucin RNA isoform panels capturing the heterogeneity of the IBD patient population and showing great potential to indicate barrier function in IBD patients.