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

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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.

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Acknowledgments

This work was supported by NIH/NIDCR Grant 5P20RR020145 to M.E.C.B. and R.I.A.; NIH Grant AI069027 (and an associated American Recovery and Reinvestment Act supplement) and a Senior Research Award from the Crohn’s and Colitis Foundation of America (CCFA) to C.S.K.

Conflict of interest

None.

Author information

Author notes

  1. Maria E. C. Bruno

    Present address: Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA

  2. Eric W. Rogier

    Present address: Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA

  3. Razvan I. Arsenescu

    Present address: Department of Internal Medicine, The Ohio State University, Columbus, OH, USA

  4. Cathryn J. Kurkjian

    Present address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Drive, Chapel Hill, NC, 27599, USA

  5. Gavin I. Ellis

    Present address: Department of Microbiology, Perelman School of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA

Authors and Affiliations

  1. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA

    Maria E. C. Bruno, Eric W. Rogier, Cathryn J. Kurkjian, Gavin I. Ellis & Charlotte S. Kaetzel

  2. Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA

    Razvan I. Arsenescu & Deborah R. Flomenhoft

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  1. Maria E. C. Bruno
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Correspondence to Charlotte S. Kaetzel.

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Bruno, M.E.C., Rogier, E.W., Arsenescu, R.I. et al. Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn’s Disease and Ulcerative Colitis. Dig Dis Sci 60, 2976–2984 (2015). https://doi.org/10.1007/s10620-015-3700-2

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