Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn's Disease and Ulcerative Colitis

Dig Dis Sci. 2015 Oct;60(10):2976-84. doi: 10.1007/s10620-015-3700-2. Epub 2015 May 9.

Abstract

Background: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation due to immunological, microbial, and environmental factors in genetically predisposed individuals. Advances in the diagnosis, prognosis, and treatment of IBD require the identification of robust biomarkers that can be used for molecular classification of diverse disease presentations. We previously identified five genes, RELA, TNFAIP3 (A20), PIGR, TNF, and IL8, whose mRNA levels in colonic mucosal biopsies could be used in a multivariate analysis to classify patients with CD based on disease behavior and responses to therapy.

Aim: We compared expression of these five biomarkers in IBD patients classified as having CD or UC, and in healthy controls.

Results: Patients with CD were characterized as having decreased median expression of TNFAIP3, PIGR, and TNF in non-inflamed colonic mucosa as compared to healthy controls. By contrast, UC patients exhibited decreased expression of PIGR and elevated expression of IL8 in colonic mucosa compared to healthy controls. A multivariate analysis combining mRNA levels for all five genes resulted in segregation of individuals based on disease presentation (CD vs. UC) as well as severity, i.e., patients in remission versus those with acute colitis at the time of biopsy.

Conclusion: We propose that this approach could be used as a model for molecular classification of IBD patients, which could further be enhanced by the inclusion of additional genes that are identified by functional studies, global gene expression analyses, and genome-wide association studies.

Keywords: Colonic mucosa; Crohn’s disease; Multivariate analysis; Ulcerative colitis; mRNA biomarkers.

Publication types

  • Comparative Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chi-Square Distribution
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / genetics*
  • Crohn Disease / pathology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression
  • Genetic Markers
  • Humans
  • Interleukin-8 / genetics*
  • Intestinal Mucosa / pathology
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phenotype
  • RNA, Messenger / genetics*
  • Receptors, Polymeric Immunoglobulin / genetics*
  • Transcription Factor RelA / genetics*
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Necrosis Factor-alpha / genetics
  • Young Adult

Substances

  • CXCL8 protein, human
  • DNA-Binding Proteins
  • Genetic Markers
  • Interleukin-8
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RELA protein, human
  • RNA, Messenger
  • Receptors, Polymeric Immunoglobulin
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3