Introduction

In this study we have exploited the recent development of methods that have enabled the analysis of RNA present in urine exosomes of prostate cancer (PCa) patients. We report RNA expression patterns that contain diagnostic and prognostic information for PCa, and association with response to hormone treatment.

Methods

First catch urine following digital rectal examination were collected from 800 men. 3 groups of patients were used: Low, Intermediate, and High-risk according to NICE stratification criteria, and two control groups: benign and advanced disease. 50-gene transcript expression analysis using NanoString technology was performed on 193 samples. Exosomal RNA Next-Generation Sequencing was performed on 20 samples for novel biomarker discovery.

Results

Expression analysis identified transcripts that were significantly differential expressed: 17 between cancer and non-cancer samples, and another 17 transcripts up-regulated in high-risk and advanced disease in comparison to lower-grade disease.

Two gene transcripts were significantly differentially expressed in patients who failed to respond to hormone treatment for high risk/metastatic disease. Three genes were significantly differentially expressed in patients who relapsed within 12-months of treatment initiation.

Next-Generation Sequencing of exosomal RNA samples identified 45 genes to be significantly differentially expressed between non-cancer and cancer samples.  33 out of the 45 genes showed a significant linear trend in association with cancer-risk.

Conclusions

Urine exosomal RNA contains PCa- specific transcripts. Gene expression analysis and Next Generation Sequencing identified genes that are significantly differentially expressed between cancer and non-cancer cases as well as prognostic genes and genes that can predict response to hormone treatment.