title: Colorectal cancers with microsatellite instability display unique miRNA profiles.
abstract: OBJECTIVE
  microRNAs (miRNA) are small noncoding transcripts that play an important role in carcinogenesis. miRNA expression profiles have been shown to discriminate between different types of cancers. The aim of this study was to analyze global miRNA signatures in various groups of colorectal cancers (CRC) based on the presence of microsatellite instability (MSI).
  
  
  METHODS
  We analyzed genome-wide miRNA expression profiles in 54 CRC tissues [22 with Lynch syndrome, 13 with sporadic MSI due to MLH1 methylation, 19 without MSI (or microsatellite stable, MSS)] and 20 normal colonic tissues by miRNA microarrays. Using an independent set of MSI-positive samples (13 with Lynch syndrome and 20 with sporadic MSI), we developed a miRNA-based predictor to differentiate both types of MSI by quantitative reverse transcriptase PCR.
  
  
  RESULTS
  We found that the expression of a subset of nine miRNAs significantly discriminated between tumor and normal colonic mucosa tissues (overall error rate = 0.04). More importantly, Lynch syndrome tumors displayed a unique miRNA profile compared with sporadic MSI tumors; miR-622, miR-1238, and miR-192 were the most differentially expressed miRNAs between these two groups. We developed a miRNA-based predictor capable of differentiating between types of MSI in an independent sample set.
  
  
  CONCLUSIONS
  CRC tissues show distinct miRNA expression profiles compared with normal colonic mucosa. The discovery of unique miRNA expression profiles that can successfully discriminate between Lynch syndrome, sporadic MSI, and sporadic MSS colorectal cancers provides novel insights into the role of miRNAs in colorectal carcinogenesis, which may contribute to the diagnosis, prognosis, and treatment of this disease.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, Texas 75246, USA.
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.forename: Leticia
authors.initials: L
authors.lastname: Moreira
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Lozano
authors.forename: Alexander
authors.initials: A
authors.lastname: Link
authors.forename: Georgina
authors.initials: G
authors.lastname: Ramirez
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Miriam
authors.initials: M
authors.lastname: Cuatrecasas
authors.forename: Mildred
authors.initials: M
authors.lastname: Arnold
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
authors.forename: Sapna
authors.initials: S
authors.lastname: Syngal
authors.forename: Elena
authors.initials: E
authors.lastname: Stoffel
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Jover
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
authors.forename: Meritxell
authors.initials: M
authors.lastname: Gironella
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D003937:Diagnosis, Differential; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D053842:Microsatellite Instability; D040081:Protein Array Analysis; D054928:Validation Studies as Topic
chemical_list: D035683:MicroRNAs