title: Diagnostic and prognostic microRNAs in stage II colon cancer.
abstract: MicroRNAs (miRNA) are a class of small noncoding RNAs with important posttranscriptional regulatory functions. Recent data suggest that miRNAs are aberrantly expressed in many human cancers and that they may play significant roles in carcinogenesis. Here, we used microarrays to profile the expression of 315 human miRNAs in 10 normal mucosa samples and 49 stage II colon cancers differing with regard to microsatellite status and recurrence of disease. Several miRNAs were differentially expressed between normal tissue and tumor microsatellite subtypes, with miR-145 showing the lowest expression in cancer relative to normal tissue. Microsatellite status for the majority of cancers could be correctly predicted based on miRNA expression profiles. Furthermore, a biomarker based on miRNA expression profiles could predict recurrence of disease with an overall performance accuracy of 81%, indicating a potential role of miRNAs in determining tumor aggressiveness. The expression levels of miR-320 and miR-498, both included in the predictive biomarker, correlated with the probability of recurrence-free survival by multivariate analysis. We successfully verified the expression of selected miRNAs using real-time reverse transcription-PCR assays for mature miRNAs, whereas in situ hybridization was used to detect the accumulation of miR-145 and miR-320 in normal epithelial cells and adenocarcinoma cells. Functional studies showed that miR-145 potently suppressed growth of three different colon carcinoma cell lines. In conclusion, our results suggest that perturbed expression of numerous miRNAs in colon cancer may have a functional effect on tumor cell behavior, and, furthermore, that some miRNAs with prognostic potential could be of clinical importance.
authors.affiliation: Department of Clinical Biochemistry, Molecular Diagnostic Laboratory, Aarhus University Hospital, Aarhus N, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Schepeler
authors.forename: Jørgen T
authors.initials: JT
authors.lastname: Reinert
authors.forename: Marie S
authors.initials: MS
authors.lastname: Ostenfeld
authors.forename: Lise L
authors.initials: LL
authors.lastname: Christensen
authors.forename: Asli N
authors.initials: AN
authors.lastname: Silahtaroglu
authors.forename: Lars
authors.initials: L
authors.lastname: Dyrskjøt
authors.forename: Carsten
authors.initials: C
authors.lastname: Wiuf
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Sørensen
authors.forename: Mogens
authors.initials: M
authors.lastname: Kruhøffer
authors.forename: Søren
authors.initials: S
authors.lastname: Laurberg
authors.forename: Sakari
authors.initials: S
authors.lastname: Kauppinen
authors.forename: Torben F
authors.initials: TF
authors.lastname: Ørntoft
authors.forename: Claus L
authors.initials: CL
authors.lastname: Andersen
mesh_terms: D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C578093:MIRN498 microRNA, human; D035683:MicroRNAs