miRNA Signatures of Indolent and Aggressive Prostate Cancer
Louise Flynn, Orla Sheils, John J O'Leary, Stephen P Finn, William Watson, Massimo Loda, Lorelei Mucci. University of Dublin, Trinity College, Dublin, Ireland; University College Dublin, Dublin, Ireland; Dana Farber Cancer Institute, Boston, MA; Harvard School of Public Health, Boston, MA
Background: With the advent of active surveillance there is an increasing need for biomarkers to more accurately stratify patients and avoid unnecessary radical treatment in a proportion of patients. Aberrant miRNA expression has for some time been postulated to be involved in the development and subsequent progression of prostate cancer. Taking this into account, a fundamental aim of the Prostate Cancer Research Consortium has been to identify specific miRNA signatures for distinction between clinically significant and insignificant disease and eventually to integrate miRNA signatures with other tumor-specific features. Here we report the results of an initial feasibility study showing the differential expression of a pre-defined profile of biologically relevant miRNAs in a cohort of putatively indolent and biologically significant prostatectomy patient specimens.
Design: Prostatectomy cases were segregated into putatively indolent and aggressive based on Epstein's Criteria for the identification of insignificant prostate cancer. Cores were removed from the tumour areas within the FFPE blocks, and RNA was subsequently extracted. Expression analysis was carried out using standard TaqMan chemistry, incorporating a preamplification step.
Results: The biologically significant cohort of patient samples exhibits a miRNA profile distinct from that observed in the indolent cohort. The expression of four miRNAs (miR141, miR146a, miR200b and miR20a) is significantly upregulated (p<0.05) in the biologically significant group when compared to the indolent cohort. A larger number approach significance (miR222, miR126, miR13a, miR330, miR125b, miR101, miR21, miR221, miR15a, miR16-1, miR331) and will be taken forward in a larger validation study.
Conclusions: A distinct miRNA expression profile exists in biologically significant cases of prostate cancer, which may be used to accurately distinguish between insignificant and significant cases within a clinical setting. These miRNAs possess well defined roles in the progression of prostate cancer, including the promotion of metastasis and anti-apoptotic effects.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 123, Wednesday Morning