Prostate-derived circulating microRNAs add prognostic value to prostate cancer risk calculators

Abstract

Prostate cancer is the second leading cause of malignancy-related deaths among American men; however, hundreds of thousands of men live with indolent disease. Active surveillance is a safe option for men with low-risk disease. Many patients are treated with radical prostatectomy or radiation therapy, both of which have associated morbidity. Herein, we sought to identify prostate-derived microRNAs in patient sera and serum extracellular vesicles, and determine if those microRNAs added to current clinical nomograms for prostate cancer prognosis pre- and post-biopsy. Intracellular and extracellular vesicle-contained microRNAs from prostate cancer patient samples were profiled by next-generation RNA sequencing. Abundant microRNAs were included in a custom microRNA PCR panel that was queried in whole serum and serum extracellular vesicles from a diverse cohort of men diagnosed with prostate cancer. Statistical modeling showed that the levels of these circulating microRNAs significantly differed between indolent and aggressive disease and added prognostic value to pretreatment nomograms for prostate cancer disease risk. The microRNAs within the extracellular vesicles had improved prognostic value compared to the microRNAs in the whole serum. In summary, quantifying microRNAs circulating in extracellular vesicles is a clinically feasible assay that may provide additional information for assessing prostate cancer risk stratification.