title: MicroRNAs Classify Different Disease Behavior Phenotypes of Crohn's Disease and May Have Prognostic Utility.
abstract: BACKGROUND
  There is a dire need for reliable prognostic markers that can guide effective therapeutic intervention in Crohn's disease (CD). We examined whether different phenotypes in CD can be classified based on colonic microRNA (miRNA) expression and whether miRNAs have prognostic utility for CD.
  
  
  METHODS
  High-throughput sequencing of small and total RNA isolated from colon tissue from patients with CD and controls without Inflammatory Bowel Disease (non-IBD) was performed. To identify miRNAs associated with specific phenotypes of CD, patients were stratified according to disease behavior (nonstricturing, nonpenetrating; stricturing; penetrating), and miRNA profiles in each subset were compared with those of the non-IBD group. Validation assays were performed using quantitative reverse transcription polymerase chain reaction. These miRNAs were further evaluated by quantitative reverse transcriptase polymerase chain reaction on formalin-fixed, paraffin-embedded tissue (index biopsies) of patients with nonpenetrating CD at the time of diagnosis that either retained the nonpenetrating phenotype or progressed to penetrating/fistulizing CD.
  
  
  RESULTS
  We found a suite of miRNAs, including miR-31-5p, miR-215, miR-223-3p, miR-196b-5p, and miR-203 that stratify patients with CD according to disease behavior independent of the effect of inflammation. Furthermore, we also demonstrated that expression levels of miR-215 in index biopsies of patients with CD might predict the likelihood of progression to penetrating/fistulizing CD. Finally, using a novel statistical simulation approach applied to colonic RNA-sequencing data for patients with CD and non-IBD controls, we identified miR-31-5p and miR-203 as candidate master regulators of gene expression profiles associated with CD.
  
  
  CONCLUSIONS
  miRNAs may serve as clinically useful prognostic markers guiding initial therapy and identifying patients who would benefit most from effective intervention.
authors.affiliation: *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; †Department of Medicine, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; ‡Department of Medicine, Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; §Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Departments of ||Pathology and ¶Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; **Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and ††Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Bailey C E
authors.initials: BC
authors.lastname: Peck
authors.forename: Matthew
authors.initials: M
authors.lastname: Weiser
authors.forename: Saangyoung E
authors.initials: SE
authors.lastname: Lee
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Gipson
authors.forename: Vishal B
authors.initials: VB
authors.lastname: Iyer
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Sartor
authors.forename: Hans H
authors.initials: HH
authors.lastname: Herfarth
authors.forename: Millie D
authors.initials: MD
authors.lastname: Long
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hansen
authors.forename: Kim L
authors.initials: KL
authors.lastname: Isaacs
authors.forename: Dimitri G
authors.initials: DG
authors.lastname: Trembath
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbar
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Sadiq
authors.forename: Terrence S
authors.initials: TS
authors.lastname: Furey
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
authors.forename: Shehzad Z
authors.initials: SZ
authors.lastname: Sheikh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000302:isolation & purification / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs