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

IF 2.5 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Digestive Diseases and Sciences Pub Date : 2024-08-31 DOI:10.1007/s10620-024-08595-3
Kevin A Chen, Valerie Gartner, Kimberly C Darlington, Sophie R Silverstein, Meaghan M Kennedy Ng, Logan Butler, Kelli Avalos, Nina C Nishiyama, Chinmaya U Joisa, Matthew R Schaner, Grace Lian, Caroline Beasley, Gwen W Lau, Mikaela J Bauer, Lee-Ching Zhu, Muneera R Kapadia, Shawn M Gomez, Terrence S Furey, Shehzad Z Sheikh
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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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术后克罗恩病复发与感染并发症:转录组分析
背景:克罗恩病(CD)是一种影响胃肠道的慢性炎症,以狭窄、瘘管和肿瘤等并发症为特征。尽管医疗技术在不断进步,但仍有大量克罗恩病患者需要接受手术治疗,而且许多患者会出现术后并发症和复发。以往的研究通过分析基因表达来独立研究复发和术后并发症。本研究旨在找出复发和术后并发症的重叠差异表达基因和通路:方法:分析了45名克罗恩病患者的数据集,包括回肠和结肠组织的基因表达、内镜复发和腹腔内化脓性并发症。基因组富集分析用于确定与结果相关的基因通路。最后,建立了一个多变量逻辑回归模型,以评估基因通路是否与这两种结果独立相关:结果:在回肠组织中,包括干扰素α和γ反应在内的几种炎症通路在内镜复发和腹腔内脓毒症并发症患者中上调。此外,上皮间质转化途径也出现上调。在结肠组织中,肌生成和氧化磷酸化等代谢过程在两种结果中均出现下调。在多变量模型中,结肠组织肌生成的下调与内镜复发和腹腔内脓毒症并发症均有显著相关性:这些发现揭示了这些结果的生物学基础,并提出了减少这些结果发生的潜在生物标志物或治疗靶点。为了证实这些结果并改善克罗恩病患者的术后效果,有必要进行进一步的验证和多机构研究。
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来源期刊
Digestive Diseases and Sciences
Digestive Diseases and Sciences 医学-胃肠肝病学
CiteScore
6.40
自引率
3.20%
发文量
420
审稿时长
1 months
期刊介绍: Digestive Diseases and Sciences publishes high-quality, peer-reviewed, original papers addressing aspects of basic/translational and clinical research in gastroenterology, hepatology, and related fields. This well-illustrated journal features comprehensive coverage of basic pathophysiology, new technological advances, and clinical breakthroughs; insights from prominent academicians and practitioners concerning new scientific developments and practical medical issues; and discussions focusing on the latest changes in local and worldwide social, economic, and governmental policies that affect the delivery of care within the disciplines of gastroenterology and hepatology.
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