Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer

Abstract

PurposeThe analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans.Experimental DesignThe ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2.ResultsIn this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560–0.788), ERG (AUC 0.785 (CI:0.680–0.890), PCA3 (AUC 0.681 (CI:0.567–0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600–0.888), and TMPRSS2 (AUC 0.637 (CI:0.519–0.754).ConclusionThis pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

Emerging Variants of Castration-Resistant Prostate Cancer

“…Urine is another source of tumor cell DNA and was also recently exploited for whole genome sequencing at different stages, before or after ADT in hormone sensitive disease as well as post-docetaxel chemotherapy in CRPC patients [81]. Urine [82] or blood exosome, oncosomes [83], or microvesicles (extracellular vesicles) have also been introduced as a non-invasive platform for studying gene expression changes reflective of primary or metastatic prostate tissue. How these alternative technologies may apply to the detection of CRPC variants and/or other resistance pathways and the best timing and cohorts to evaluate warrant further investigation.…”

Vesicle-MaNiA: extracellular vesicles in liquid biopsy and cancer

“…This observation could open a new avenue on non-invasive characterization of transcriptional alterations with prognostic or therapeutic implications. Indeed, urine exosome gene expression has been recently proposed as a novel non-invasive approach to differentiate patients with higher-grade prostate cancer among men with elevated PSA levels, thus reducing the number of unnecessary biopsies [43]. …”

The role of extracellular vesicle microRNAs in cancer biology

“…Unauthenticated Download Date | 5/11/18 6:13 PM bladder cancer patients. Since urinary exosomes are a noninvasive source, combinatorial methods designed to detect simultaneously urinary miRNAs and lncRNA might provide a more precise and simple approach for the diagnosis of prostate and bladder cancers [83].…”