Abstract 3049: Overexpression of miR-17 family miRNAs in prostate cancer biopsies: Evidence for a stem-cell-like miRNA profile in high grade/high stage tumors

Abstract

Abstract Complex changes in microRNA (miRNA) expression patterns have been observed in many different types of cancer, including prostate cancer. Although the consequences of deregulation of miRNA expression in human cancer are still largely unknown, the use of miRNAs for cancer classification and prognosis has emerged as an important new area of biomarker research. We compared the tissue expression of miRNAs in prostate biopsies from patients with high grade/high stage tumors with biopsies from patients with no evidence of malignancy. Snap frozen prostate biopsy samples were prospectively collected using tissue printing techniques and total RNA was isolated for miRNA analysis using Agilent miRNA microarrays (Version 1, containing 470 human tissue miRNAs). The prostate cancer cases included in the microarray profiling study had at least 5 of 12 cores positive for cancer and significant areas of Gleason 7 or more. The no-cancer controls showed no prostate cancer, HGPIN or suspicious histology in any of the 12 biopsy cores. In our analysis of miRNA expression patterns, “significant change in expression” was defined as at least 2 fold change and F test (p<0.05). Three different internal reference normalization methods were used in the data analysis; here we classify miRNAs as “overexpressed” or “underexpressed” only when all three methods agree. In high grade/high stage biopsy cancer, 64 of the 470 human tissue miRNAs on the microarray (13.6%) were found to be significantly overexpressed when compared with miRNA expression in biopsies from no-cancer controls. This set of overexpressed miRNAs includes 4 of the 5 miR-200 family miRNAs that have been implicated in the regulation of the epithelial-to-mesenchymal transition (EMT). The cancer-overexpressed miRs also include 6 of the 8 miR-17 family genes; this miRNA family has been implicated in the control of stem-cell differentiation during embryogenesis. Interestingly, the 6 miR-17 family miRs that are overexpressed in high grade/high stage prostate cancer include 2 from each of the 3 polycistronic clusters that encode this highly conserved miR family, an expression pattern similar to the coordinated expression observed in early embryonic development. This robust stem-cell-like miRNA profile offers an interesting new candidate biomarker that may be particularly sensitive to an aggressive prostate cancer phenotype. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3049.