TY - JOUR
T1 - Elevated colonic mucin expression correlates with extended time to surgery for ulcerative colitis patients
AU - Eshelman, Melanie A.
AU - Jeganathan, N. Arjun
AU - Schieffer, Kathleen M.
AU - Kline, Bryan P.
AU - Mendenhall, Megan
AU - Deiling, Sue
AU - Harris, Leonard
AU - Koltun, Walter A.
AU - Yochum, Gregory S.
N1 - Publisher Copyright:
© 2019, Romanian Society of Gastroenterology. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Background & Aims: Both genetic and environmental factors contribute to the development and persistence of ulcerative colitis (UC). As supported by differential responses to therapy, multiple subclasses of disease likely comprise UC. We reasoned that profiling the colonic transcriptomes may offer one approach to molecular subtype UC. Methods: We conducted RNA-sequencing (RNA-seq) on full-thickness colonic tissues from 26 UC patients undergoing colectomy. Hierarchal clustering from transcriptomic data identified disease subsets. Subsets were characterized using differential gene expression analysis, cell type deconvolution, and network analysis. Results: We identified two UC subsets that were distinguished by 957 differentially expressed genes. Cluster 1 was enriched in genes associated with intestinal epithelial cell (IEC) differentiation, while cluster 2 was enriched in genes associated with epithelial-to-mesenchymal transition (EMT) and inflammatory responses. Cluster 1 was associated with an extended time from diagnosis to colectomy [hazard ratio = 0.45 (95% CI: 0.14-0.88); p=0.03]. Of cluster 1 genes, elevated MUC5B, MUC4, and MUC2 expression displayed the strongest correlation with increased time to surgery [hazard ratio = 0.37 (95% CI: 0.11-0.61); p=0.0044]. Conclusions: Our transcriptome analysis indicates that UC can be sub-classified into at least two molecular signatures. We found that elevated mucin gene expression correlated with prolonged time to colectomy following diagnosis. This work identified MUC5B, MUC4, and MUC2 as potential prognostic indicators of disease severity, as reflected in time to surgery after diagnosis.
AB - Background & Aims: Both genetic and environmental factors contribute to the development and persistence of ulcerative colitis (UC). As supported by differential responses to therapy, multiple subclasses of disease likely comprise UC. We reasoned that profiling the colonic transcriptomes may offer one approach to molecular subtype UC. Methods: We conducted RNA-sequencing (RNA-seq) on full-thickness colonic tissues from 26 UC patients undergoing colectomy. Hierarchal clustering from transcriptomic data identified disease subsets. Subsets were characterized using differential gene expression analysis, cell type deconvolution, and network analysis. Results: We identified two UC subsets that were distinguished by 957 differentially expressed genes. Cluster 1 was enriched in genes associated with intestinal epithelial cell (IEC) differentiation, while cluster 2 was enriched in genes associated with epithelial-to-mesenchymal transition (EMT) and inflammatory responses. Cluster 1 was associated with an extended time from diagnosis to colectomy [hazard ratio = 0.45 (95% CI: 0.14-0.88); p=0.03]. Of cluster 1 genes, elevated MUC5B, MUC4, and MUC2 expression displayed the strongest correlation with increased time to surgery [hazard ratio = 0.37 (95% CI: 0.11-0.61); p=0.0044]. Conclusions: Our transcriptome analysis indicates that UC can be sub-classified into at least two molecular signatures. We found that elevated mucin gene expression correlated with prolonged time to colectomy following diagnosis. This work identified MUC5B, MUC4, and MUC2 as potential prognostic indicators of disease severity, as reflected in time to surgery after diagnosis.
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U2 - 10.15403/jgld-250
DO - 10.15403/jgld-250
M3 - Article
C2 - 31826065
AN - SCOPUS:85076399350
SN - 1841-8724
VL - 28
SP - 405
EP - 413
JO - Journal of Gastrointestinal and Liver Diseases
JF - Journal of Gastrointestinal and Liver Diseases
IS - 4
ER -