MicroRNAs as predictors and therapy for prostate cancer

Abstract

Prostate cancer (PC) is the most common neoplasia among males from developed countries and the second leading cause of death from cancer in these males. During the last years, serum prostate specific antigen (PSA) has been used as biomarker for PC diagnosis. Although PSA test has increased PC detection, it has a low specificity and leads to over-diagnosis and over-treatment; therefore, it is necessary to improve the current diagnostic methods for PC. In the past decade, urine has received more and more attention for its simplicity, as well as its potential use in identifying new biomarkers as non-invasive detection method. Deregulation of microRNAs (miRNAs) in serum/plasma or tissue has been associated with many diseases including PC, suggesting the possible use of miRNAs as diagnostic biomarkers also in other body fluids. The intent of my PhD research program was to evaluate if miRNAs known to be deregulated in blood or tissue for PC could also be detected in urine from cellular fraction, and characterize the function of the most promising of them. By analysing a large cohort of post-digital rectal exam (DRE) urine samples, we have validated a miRNA panel consisting of 3 urinary miRNAs (miR-648, miR-147b and miR-193a-5p) with a predictive value of area under the curve (AUC): 0,74 In addition, we have determined that miRNAs-miR-28 and miR-210 are under-expressed in PC urine and associated with PC development and progression, mainly affecting PC cell proliferation and migration. Overall, this work introduces novel candidate miRNAs that are aberrantly expressed in PC as diagnostic biomarkers, and perhaps aids in defining how miRNAs might one day serve as anti-cancer therapeutic agents.