title: The rectal cancer microRNAome--microRNA expression in rectal cancer and matched normal mucosa.
abstract: OBJECTIVE
  miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.
  
  
  METHODS
  Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR.
  
  
  RESULTS
  Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference >0.5 and P < 0.001) between rectal cancer and normal rectal mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients.
  
  
  CONCLUSIONS
  This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways for therapeutic exploitation.
authors: Department of General and Visceral Surgery, Medical Statistics, University Medical Center, Göttingen, Germany.
authors: Jochen
authors: J
authors: Gaedcke
authors: Marian
authors: M
authors: Grade
authors: Jordi
authors: J
authors: Camps
authors: Rolf
authors: R
authors: Søkilde
authors: Bogumil
authors: B
authors: Kaczkowski
authors: Aaron J
authors: AJ
authors: Schetter
authors: Michael J
authors: MJ
authors: Difilippantonio
authors: Curtis C
authors: CC
authors: Harris
authors: B Michael
authors: BM
authors: Ghadimi
authors: Søren
authors: S
authors: Møller
authors: Tim
authors: T
authors: Beissbarth
authors: Thomas
authors: T
authors: Ried
authors: Thomas
authors: T
authors: Litman
mesh_terms: D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results
chemical_list: C544965:MIRN135 microRNA, human; D035683:MicroRNAs