title: Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia.
abstract: BACKGROUND
  It is unknown why patients with extensive ulcerative colitis (UC) have a higher risk of colorectal cancer compared with patients with left-sided UC. This study characterizes the inflammatory processes in left-sided UC, pancolitis, and UC-associated dysplasia at the transcriptional level to identify potential biomarkers and transcripts of importance for the carcinogenic behavior of chronic inflammation.
  
  
  METHODS
  The Affymetrix GeneChip Human Genome U133 Plus 2.0 was applied on colonic biopsies from UC patients with left-sided UC, pancolitis, dysplasia, and controls. Reverse transcription polymerase chain reaction and immunohistochemistry were performed for validating selected transcripts in the initial cohort and in 2 independent cohorts of patients with UC. Microarray data were analyzed by principal component analysis, and reverse transcription polymerase chain reaction and immunohistochemistry data by the Wilcoxon's rank-sum test.
  
  
  RESULTS
  The principal component analysis results revealed separate clusters for left-sided UC, pancolitis, dysplasia, and controls. Close clustering of dysplastic and pancolitic samples indicated similarities in gene expression. Indeed, 101 and 656 parallel upregulated and downregulated transcripts, respectively, were identified in specimens from dysplasia and pancolitis. Validation of selected transcripts hereof identified insulin receptor alpha (INSRA) and MAP kinase interacting serine/threonine kinase 2 (MKNK2) with an enhanced expression in dysplasia compared with left-sided UC and controls, whereas laminin γ2 (LAMC2) was found with a lower expression in dysplasia compared with the remaining 3 groups.
  
  
  CONCLUSIONS
  This study demonstrates pancolitis and left-sided UC as distinct inflammatory processes at the transcriptional level, and identifies INSRA, MKNK2, and LAMC2 as potential critical transcripts in the inflammation-driven preneoplastic process of UC.
authors.affiliation: *Department of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen, Copenhagen, Denmark; †Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; ‡Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark; §Health Care Evaluation Unit, Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland; ‖Division of Experimental Pathology, Institute of Pathology, Division of Immunopathology, University of Bern, Bern, Switzerland; and ¶Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Jacob T
authors.initials: JT
authors.lastname: Bjerrum
authors.forename: Ole H
authors.initials: OH
authors.lastname: Nielsen
authors.forename: Lene B
authors.initials: LB
authors.lastname: Riis
authors.forename: Valerie
authors.initials: V
authors.lastname: Pittet
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Jørgen
authors.initials: J
authors.lastname: Olsen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D003092:Colitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003093:Colitis, Ulcerative / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger