Post-operative Crohn’s Disease Recurrence and Infectious Complications: A Transcriptomic Analysis

克罗恩病 医学 回肠 转录组 疾病 肝病学 内科学 炎症性肠病 胃肠病学 下调和上调 胃肠道 并发症 基因表达 基因 生物 生物化学
作者
Kevin A. Chen,Valerie Gartner,Kimberly Darlington,Sophie Silverstein,Meaghan M. Kennedy Ng,Logan Butler,Kelli Avalos,Nina C. Nishiyama,Chinmaya U. Joisa,Matthew R. Schaner,Grace Lian,Caroline Beasley,Gwen Lau,Mikaela Bauer,Lee‐Ching Zhu,Muneera R. Kapadia,Shawn M. Gomez,Terrence S. Furey,Shehzad Z. Sheikh
出处
期刊:Digestive Diseases and Sciences [Springer Nature]
标识
DOI:10.1007/s10620-024-08595-3
摘要

Crohn's disease (CD) is a chronic inflammatory condition affecting the gastrointestinal tract, characterized by complications such as strictures, fistulas, and neoplasia. Despite medical advancements, a significant number of patients with Crohn's disease require surgery, and many experience post-operative complications and recurrence. Previous studies have analyzed gene expression to study recurrence and post-operative complications independently. This study aims to identify overlapping differentially expressed genes and pathways for recurrence and post-operative complications. A dataset including 45 patients with Crohn's disease, including gene expression from ileum and colon tissue, endoscopic recurrence, and intra-abdominal septic complications was analyzed. Gene set enrichment analysis was used to identify gene pathways associated with the outcomes. Finally, a multi-variable logistic regression model was created to assess whether gene pathways were independently associated with both outcomes. In ileum tissue, several inflammatory pathways, including interferon alpha and gamma response were upregulated in patients with endoscopic recurrence and intra-abdominal septic complications. In addition, there was upregulation of the epithelial mesenchymal transition pathway. In colon tissue, metabolic processes, such as myogenesis and oxidative phosphorylation were downregulated in both outcomes. In a multivariate model, downregulation of myogenesis in colon tissue was significantly associated with both endoscopic recurrence and intra-abdominal septic complications. These findings shed light on the underlying biology of these outcomes and suggest potential biomarkers or therapeutic targets to reduce their occurrence. Further validation and multi-institutional studies are warranted to confirm these results and improve post-operative outcomes for patients with Crohn's disease.
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