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

e15553 Background: Prostate cancer is one of the most common cancers in men, with approximately 10% of all new cancer cases and ~5% of all cancer deaths in 2019. The standard test for prostate cancer is the Prostate Serum Antigen (PSA) test. The PSA test suffers from low specificity (20-40%) in patients including ‘grey zone’ levels (4-10 ng/mL); moreover, the PSA test fails to identify patients with high-risk cancers. Previously we developed ExoDx Prostate Intelliscore (EPI), a urine-based exosome prostate cancer test optimized to rule out the need for a biopsy (risk stratification for high-grade prostate cancer). This study utilized a next generation exosome-based test that specifically enriches a subtype of prostate cancer exosomes from urine. Early detection of prostate cancer via a non-invasive method is desirable and the identification of patients with high-risk cancer is critical. Here we describe the development of a prostate-specific urinary exosome test for the identification of patients with prostate cancer. Methods: We have developed a prostate-specific enrichment method to isolate exosomes of prostate origin from urine samples. Using an affinity-based method against surface marker proteins found on prostate cells, we were able to selectively enrich for exosomes shed by the prostate gland with demonstrated specificity. Subsequent analysis of exosomal nucleic acids enables a promising panel of gene expression biomarkers capable of distinguishing patients with prostate cancer from healthy individuals. Results: RNA from prostate cancer enriched exosomes was compared to total exosomes from urine. Enrichment of prostate cancer specific exosomes significantly enhanced the RNA signature compared to total urine exosomes. Conclusions: Prostate cancer tests have recently been developed for RNA signatures in urine. Exosomes provide a source of nucleic acids as they are actively shed continuously from living cells as part of their normal life cycle. The urine exosomes can be used for total RNA transcriptome analysis and are therefore a very rich source of biomarkers for prostate cancer that can be tailored to different clinical indications. An affinity-based enrichment for tissue-specific exosomes allow for better resolution of the gene expression profile from the tissue of interest and reduces the RNA targets from non-relevant processes of the bladder and kidneys. The gene signature identified in this ongoing study could potentially provide a non-invasive molecular means for the early diagnosis of prostate cancer.

Download Full-text

Novel non-invasive urine-based gene expression assay discriminates between low- and high-risk prostate cancer before biopsy

Translational Cancer Research ◽

10.21037/tcr.2016.07.21 ◽

2016 ◽

Vol 5 (S2) ◽

pp. S286-S289

Author(s):

Malte W. Vetterlein ◽

Quoc-Dien Trinh ◽

Felix K. H. Chun

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

High Risk ◽

Non Invasive ◽

Gene Expression Assay ◽

High Risk Prostate Cancer ◽

Risk Prostate Cancer

Download Full-text

Prognostic significance of the evaluation of expression of the gene PCA3 in urine in patients with localized prostate cancer and histomorphological changes in the peritumoral zone

Urologicheskie vedomosti ◽

10.17816/uroved8311-19 ◽

2018 ◽

Vol 8 (3) ◽

pp. 11-19

Author(s):

Philip S. Bova

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Biochemical Recurrence ◽

Prognostic Significance ◽

Intraepithelial Neoplasia ◽

Disease Recurrence ◽

Localized Prostate Cancer ◽

Urine Sediment ◽

Increased Risk ◽

Urine Exosomes

Aim. To determine the prognostic significance PCA3 gene expression in urine sediment and exosomes in patients with localized prostate cancer (PC) and associated histologic changes in the peritumoral zone as a predictor of biochemical recurrence after radical prostatectomy (RPE). Materials and methods. Of 148 patients with localized PC, 96 (65%) had high-grade prostatic intraepithelial neoplasia (PIN-2) in the peritumoral zone. The other 52 (35%) had no pathologic tissue of the peritumoral zone. PDA3 expression in urine sediment and exosomes was determined with real-time PCR with respect to the reference gene KLK3. Results. The PCA3 gene expression level in urine exosomes in patients with PIN-2 in the prostatic peritumoral zone and synchronous pancreatic adenocarcinoma was higher among patients with subsequent disease recurrence. Increased PCA3 gene expression in the urine sediment was also predictive of the risk of recurrence of a prostatic tumor with PIN-2 in the peritumoral zone, although to a lesser degree than the results with urine exosomes. When the ∆Ct РСА3-KLK3 was ≥1,86 in the urine sediment, biochemical recurrence of PC and PIN-2 developed more frequently in the peritumoral zone (84% versus 51%, p = 0,013). Conclusions. Increased PCA3 gene expression in urine sediment and exosomes is a predictor of increased risk of biochemical recurrence after RPE in patients with localized PC and PIN-2 in the peritumoral zone.

Download Full-text

PII-LBA2 VALIDATION OF A NOVEL NON-INVASIVE URINE EXOSOME GENE EXPRESSION ASSAY TO PREDICT HIGH-GRADE PROSTATE CANCER IN PATIENTS UNDERGOING INITIAL BIOPSY WITH AN EQUIVOCAL PSA.

The Journal of Urology ◽

10.1016/j.juro.2015.03.082 ◽

2015 ◽

Vol 193 (4S) ◽

Cited By ~ 2

Author(s):

James McKiernan ◽

Michael Donovan ◽

Vince O'Neill ◽

Stefan Bentink ◽

Mikkel Noerholm ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

High Grade ◽

Non Invasive ◽

Gene Expression Assay ◽

Initial Biopsy

Download Full-text

Gene expression profiles in prostate cancer: Identification of candidate non-invasive diagnostic markers

Actas Urológicas Españolas (English Edition) ◽

10.1016/j.acuroe.2013.12.002 ◽

2014 ◽

Vol 38 (3) ◽

pp. 143-149 ◽

Cited By ~ 1

Author(s):

L. Mengual ◽

E. Ars ◽

J.J. Lozano ◽

M. Burset ◽

L. Izquierdo ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Diagnostic Markers ◽

Non Invasive

Download Full-text

299. Non-Invasive, Quantitative Imaging of Adenovirus-Mediated Gene Expression in Humans with Prostate Cancer

Molecular Therapy ◽

10.1016/s1525-0016(16)39702-7 ◽

2008 ◽

Vol 16 ◽

pp. S112

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Quantitative Imaging ◽

Non Invasive

Download Full-text

350 Urinary detection of a five-gene expression signature for the non-invasive diagnosis of prostate cancer

European Urology Supplements ◽

10.1016/s1569-9056(14)60345-6 ◽

2014 ◽

Vol 13 (1) ◽

pp. e350

Author(s):

L. Mengual ◽

J.J. Lozano ◽

M. Ingelmo-Torres ◽

L. Izquierdo ◽

M. Ribal ◽

...

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Gene Expression Signature ◽

Expression Signature ◽

Non Invasive

Download Full-text

Initial whole blood-based gene expression profile assays in mCRPC pts.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.370 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 370-370

Author(s):

Koji Tsumagari ◽

Patrick Miller ◽

Marcus Marie Moses ◽

Elisa Ledet ◽

A. Oliver Sartor

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Whole Blood ◽

Potential Role ◽

Acquired Resistance ◽

Targeting Therapy ◽

Non Invasive ◽

Qrt Pcr ◽

Collecting Methods ◽

Small Cohort

370 Background: Although second generation androgen receptor (AR) targeting therapy, abiraterone (Abi) and enzalutamide (enza), improve therapeutic effect for patients of mCRPC, acquired resistance occurs. Biomarkers are clearly needed to predict the efficacy of AR targeting drugs for mCRPC patients and much work is occurring on this important issue. Circulating tumor cells are attractive biomaterials because of non-invasive collecting methods. In this study, we assessed whole blood RNA as a non-invasive methodology to access biomarkers of potential interest. Methods: We used whole blood (~5mL) preserved in PAXgene tubes from 10 patients (pts) with mCRPC with acquired resistance following Abi and 11 controls without prostate cancer. Total RNA was extracted followed by qRT-PCR for assessment of 10 transcripts including ARV7, HOXB13, GHLR2, KLK3, KLK2, FOXA1, SchLAP1, KIF2C, MIA, and NCAM1. All amplicons were normalized to β-actin. Results: ARV7 (2/10), GRHL2 (2/10), HOXB13 (4/10), KLK3 (7/10), and KLK2 (4/10) amplicons were detected only in the mCRPC prostate pts. FOXA1 (7/10) and SchLAP1 (3/10) amplicons were detected in mCRPC pts at higher concentrations in mCRPC pts as compared to controls ( p< 0.001 and p = 0.02, respectively). In contrast, KIF2C (5/11), MIA (11/11), and NCAM1 (11/11) amplicons were present in pts but in lower concentrations in mCRPC as compared to controls (p = 0.03, p< 0.001, and p< 0.001, respectively). Conclusions: We identified 5 transcripts that can be detected from whole blood RNA assays only from PCa pts, additional transcripts were expressed at higher or lower concentrations as compared to controls. Although this is a small cohort, these findings highlight the potential role for whole blood RNA to assess mCRPC pts.

Download Full-text