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Post-operative Crohn's Disease Recurrence and Infectious Complications: A Transcriptomic Analysis.
Chen, Kevin A; Gartner, Valerie; Darlington, Kimberly C; Silverstein, Sophie R; Kennedy Ng, Meaghan M; Butler, Logan; Avalos, Kelli; Nishiyama, Nina C; Joisa, Chinmaya U; Schaner, Matthew R; Lian, Grace; Beasley, Caroline; Lau, Gwen W; Bauer, Mikaela J; Zhu, Lee-Ching; Kapadia, Muneera R; Gomez, Shawn M; Furey, Terrence S; Sheikh, Shehzad Z.
Afiliación
  • Chen KA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Gartner V; Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, Burnett Womack Building, Suite 4038, Chapel Hill, NC, 27599, USA.
  • Darlington KC; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Silverstein SR; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Kennedy Ng MM; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Butler L; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Avalos K; Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, Burnett Womack Building, Suite 4038, Chapel Hill, NC, 27599, USA.
  • Nishiyama NC; Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, Burnett Womack Building, Suite 4038, Chapel Hill, NC, 27599, USA.
  • Joisa CU; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Schaner MR; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, 10202C Mary Ellen Jones Building, Chapel Hill, NC, 27599, USA.
  • Lian G; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Beasley C; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Lau GW; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Bauer MJ; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Zhu LC; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA.
  • Kapadia MR; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, CB #7525, Brinkhous-Bullitt Building, Chapel Hill, NC, 27599, USA.
  • Gomez SM; Department of Surgery, University of North Carolina at Chapel Hill, 100 Manning Drive, Burnett Womack Building, Suite 4038, Chapel Hill, NC, 27599, USA.
  • Furey TS; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, 10202C Mary Ellen Jones Building, Chapel Hill, NC, 27599, USA.
  • Sheikh SZ; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Bioinformatics Building; CB #7555, 130 Mason Farm Road, Chapel Hill, NC, 27599, USA. tsfurey@email.unc.edu.
Dig Dis Sci ; 2024 Aug 31.
Article en En | MEDLINE | ID: mdl-39215865
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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Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Dig Dis Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Base de datos: MEDLINE Idioma: En Revista: Dig Dis Sci Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos