Abstract
Abstract Antibody based detection of circulating prostate specific antigen (PSA) remains an important test in the diagnosis of prostate cancer. Unfortunately the test identifies a high number of false positives which require further testing to confirm the presence of cancer including several biopsies taken from the prostate itself. Whereas the performance of biopsies on individuals is associated with discomfort and risk of serious side effects, the invasive test also represents an expense to health care systems. Given the high number of false positives, the PSA test is therefore the direct cause of unnecessary suffering of healthy individuals and costs to health systems. To investigate the possibilities for developing a non-invasive and more specific test, we have developed different technologies enabling the detection of prostate cancer microRNA biomarkers in exosomes derived from urine from non-prostate massaged men. The first of these technologies is a highly sensitive LNA™-based qPCR platform for microRNA detection, which enables profiling in biofluids where microRNA levels are extremely low. At this point we have already applied this platform on thousands of biofluid samples including serum/plasma and urine to establish normal reference ranges for circulating microRNAs as well as to identify biomarkers of disease. The second technology is a simple exosome precipitation system which only requires low speed centrifugation to harvest urine exosomes. We have combined our developed technologies and applied this on cell-free urine from two different cohorts of approximately 220 patients each, to identify a number of differentially regulated microRNAs in urine from prostate cancer bearing individuals. Prostate cancer specific signatures have been obtained by different combinations of these differentially regulated microRNAs. The smallest signature is composed of two microRNAs which allows constructing receiver operating characteristic curves with areas under the curve well above 0.8. Citation Format: Peter Mouritzen, Jacob Christian Fredsøe, Thorarinn Blondal, Anne Karin Rasmussen, Michael Borre, Christa Haldrup, Ditte Andreasen, Niels Tolstrup, Torben Falck Ørntoft, Karina Dalsgaard Sørensen. A two-microRNA signature in urinary exosomes for diagnosis of prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B40.
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