Presentation Authors: Morgan Zenner*, Michael Abern, Ruben Sauer, Gayatry Mohapatra, Klara Valyi-Nagy, Larisa Nonn, Chicago, IL
Introduction: Prostate cancer remains one of the most common cancer diagnoses among men worldwide, and the risk stratification system between indolent and aggressive disease continues to evolve. Radical prostatectomy surgery (RP) is a common curative treatment option, but incontinence and erectile dysfunction are frequent side effects of the procedure. As 30-40% of low-grade patients are upgraded to higher grade at RP, many patients choose RP treatment even though they harbor indolent disease. We have previously established a serum microRNA signature that predicts prostate cancer aggressiveness in order to further stratify patients and potentially help guide treatment decisions. Our current goals are to 1) validate the serum microRNA signature in a larger cohort and 2) determine if this prognostic signature is further enriched in circulating serum exosomes. Our hypothesis is that circulating exosomes harbor an enriched microRNA prognostic signature due to selective secretion from the prostate.
Methods: Serum and serum exosomes are currently being collected from a cohort of 200 prostate cancer patients pre-RP from the University of Illinois Hospital (UIH) and the Jesse Brown VA Medical Center in order to validate the serum microRNA signature. Both sample types have been collected from 150 patients thus far. In addition, human primary prostate tissue slices and cells from RP surgery are in vitro models being used to examine the exosomal microRNAs released directly from the prostate. Small RNAs from prostate tissue, cells, and exosomes will all be sequenced by next generation sequencing and then validated by nanoString.
Results: We have assessed the presence and stability of circulating exosomal microRNAs in male serum in order to determine the potential for this test to be successfully brought to the clinic. We found that microRNAs from the prognostic signature are present in serum exosomes and that they are stable at 4Â°C, -20Â°C, and -80Â°C for up to one week. We have also detected microRNAs in exosomes from primary prostate cells and human prostate tissue slices.
Conclusions: We have discovered that serum exosomes harbor some prognostic microRNAs and may serve as a noninvasive biomarker for prostate cancer. In addition, primary prostate tissue and cells release exosomes which may enter circulation or have effects on the tumor microenvironment. We are currently working to validate the serum prognostic microRNA signature and examine the potential role of these exosomal microRNAs in prostate cancer progression.
Source of Funding: DOD CDMRP PC150495 PI: Nonn