This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schepeler, T. Articles by Andersen, C. L. Search for Related Content PubMed PubMed Citation Articles by Schepeler, T. Articles by Andersen, C. L.

Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer

¹ Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark; ² Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark; ³ Bioinformatics Research Center, University of Aarhus and ⁴ Department of Surgery P, Aarhus University Hospital, THG, Aarhus C, Denmark; and ⁵ Santaris Pharma, Hørsholm, Denmark

Requests for reprints: Claus L. Andersen, Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, DK-8200 Aarhus N, Denmark. Phone: 45-89495186; Fax: 45-89496018; E-mail: cla{at}ki.au.dk.

Key Words: colon cancer • microarray • microRNA

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. [Cancer Res 2008;68(15):6416–24]

This article has been cited by other articles:

				T Paranjape, F J Slack, and J B Weidhaas MicroRNAs: tools for cancer diagnostics Gut, November 1, 2009; 58(11): 1546 - 1554. [Abstract] [Full Text] [PDF]

				N. VALERI, C. M. CROCE, and M. FABBRI Pathogenetic and Clinical Relevance of MicroRNAs in Colorectal Cancer Cancer Genomics Proteomics, July 1, 2009; 6(4): 195 - 204. [Abstract] [Full Text] [PDF]

				L. Dyrskjot, M. S. Ostenfeld, J. B. Bramsen, A. N. Silahtaroglu, P. Lamy, R. Ramanathan, N. Fristrup, J. L. Jensen, C. L. Andersen, K. Zieger, et al. Genomic Profiling of MicroRNAs in Bladder Cancer: miR-129 Is Associated with Poor Outcome and Promotes Cell Death In vitro Cancer Res., June 1, 2009; 69(11): 4851 - 4860. [Abstract] [Full Text] [PDF]

				J. M. Friedman, G. Liang, C.-C. Liu, E. M. Wolff, Y. C. Tsai, W. Ye, X. Zhou, and P. A. Jones The Putative Tumor Suppressor microRNA-101 Modulates the Cancer Epigenome by Repressing the Polycomb Group Protein EZH2 Cancer Res., March 15, 2009; 69(6): 2623 - 2629. [Abstract] [Full Text] [PDF]

				M. Sachdeva, S. Zhu, F. Wu, H. Wu, V. Walia, S. Kumar, R. Elble, K. Watabe, and Y.-Y. Mo p53 represses c-Myc through induction of the tumor suppressor miR-145 PNAS, March 3, 2009; 106(9): 3207 - 3212. [Abstract] [Full Text] [PDF]

				F. E. AHMED, P. W. VOS, C. JEFFRIES, J. E. WILEY, D. A. WEIDNER, H. MOTA, C. BONNERUP, C. SIBATA, and R. R. ALLISON Differences in mRNA and microRNA Microarray Expression Profiles in Human Colon Adenocarcinoma HT-29 Cells Treated with either Intensity-modulated Radiation Therapy (IMRT), or Conventional Radiation Therapy (RT) Cancer Genomics Proteomics, March 1, 2009; 6(2): 109 - 127. [Abstract] [Full Text] [PDF]