title: Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn's Disease and Ulcerative Colitis.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. mebrun2@uky.edu.|Markey Cancer Center, University of Kentucky, Lexington, KY, 40536, USA. mebrun2@uky.edu.
authors.forename: Maria E C
authors.initials: ME
authors.lastname: Bruno
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. erogier@cdc.gov.|Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA. erogier@cdc.gov.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Rogier
authors.affiliation: Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA. arsenescu.1@osu.edu.|Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. arsenescu.1@osu.edu.
authors.forename: Razvan I
authors.initials: RI
authors.lastname: Arsenescu
authors.affiliation: Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA. deborah.flomenhoft@uky.edu.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Flomenhoft
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. ckurkjia@email.unc.edu.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 450 West Drive, Chapel Hill, NC, 27599, USA. ckurkjia@email.unc.edu.
authors.forename: Cathryn J
authors.initials: CJ
authors.lastname: Kurkjian
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. gavellis@mail.med.upenn.edu.|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.
authors.forename: Gavin I
authors.initials: GI
authors.lastname: Ellis
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky, Lexington, KY, 40536, USA. cskaet@uky.edu.
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Kaetzel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics*; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C498143:RELA protein, human; D012333:RNA, Messenger; D019056:Receptors, Polymeric Immunoglobulin; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
keywords: Colonic mucosa; Crohn’s disease; Multivariate analysis; Ulcerative colitis; mRNA biomarkers