Maria E C Bruno1,2, Eric W Rogier3,4, Razvan I Arsenescu5,6, Deborah R Flomenhoft7, Cathryn J Kurkjian8,9, Gavin I Ellis10,11, Charlotte S Kaetzel12. 1. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. mebrun2@uky.edu. 2. Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA. mebrun2@uky.edu. 3. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. erogier@cdc.gov. 4. Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. erogier@cdc.gov. 5. Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA. arsenescu.1@osu.edu. 6. Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. arsenescu.1@osu.edu. 7. Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA. deborah.flomenhoft@uky.edu. 8. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. ckurkjia@email.unc.edu. 9. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Drive, Chapel Hill, NC, 27599, USA. ckurkjia@email.unc.edu. 10. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. gavellis@mail.med.upenn.edu. 11. Department of Microbiology, Perelman School of Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA. gavellis@mail.med.upenn.edu. 12. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. cskaet@uky.edu.
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.
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 IBDpatients 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 IBDpatients, 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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