Gene-Transcript Expression in Urine Supernatant and Urine Cell-Sediment Are Different but Equally Useful for Detecting Prostate Cancer

Author:

Yazbek Hanna Marcelino1,Winterbone Mark2,O’Connell Shea P.2ORCID,Olivan Mireia34,Hurst Rachel2,Mills Rob5ORCID,Cooper Colin S.2,Brewer Daniel S.26ORCID,Clark Jeremy2

Affiliation:

1. Urology Department Castle Hill, Hull University Teaching Hospital, Castle Rd, Cottingham HU16 5JQ, UK

2. Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK

3. Translational Oncology Laboratory, Department of Pathology and Experimental Therapy, School of Medicine, Universitat de Barcelona, 08907 L’Hospitalet de Llobregat, Spain

4. Program of Molecular Mechanisms and Experimental Therapy in Oncology (ONCOBELL), Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Spain

5. Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK

6. Earlham Institute, Norwich NR4 7UZ, UK

Abstract

There is considerable interest in urine as a non-invasive liquid biopsy to detect prostate cancer (PCa). PCa-specific transcripts such as the TMPRSS2:ERG fusion gene can be found in both urine extracellular vesicles (EVs) and urine cell-sediment (Cell) but the relative usefulness of these and other genes in each fraction in PCa detection has not been fully elucidated. Urine samples from 76 men (PCa n = 40, non-cancer n = 36) were analysed by NanoString for 154 PCa-associated genes-probes, 11 tissue-specific, and six housekeeping. Comparison to qRT-PCR data for four genes (PCA3, OR51E2, FOLH1, and RPLP2) was strong (r = 0.51–0.95, Spearman p < 0.00001). Comparing EV to Cells, differential gene expression analysis found 57 gene-probes significantly more highly expressed in 100 ng of amplified cDNA products from the EV fraction, and 26 in Cells (p < 0.05; edgeR). Expression levels of prostate-specific genes (KLK2, KLK3) measured were ~20× higher in EVs, while PTPRC (white-blood Cells) was ~1000× higher in Cells. Boruta analysis identified 11 gene-probes as useful in detecting PCa: two were useful in both fractions (PCA3, HOXC6), five in EVs alone (GJB1, RPS10, TMPRSS2:ERG, ERG_Exons_4-5, HPN) and four from Cell (ERG_Exons_6-7, OR51E2, SPINK1, IMPDH2), suggesting that it is beneficial to fractionate whole urine prior to analysis. The five housekeeping genes were not significantly differentially expressed between PCa and non-cancer samples. Expression signatures from Cell, EV and combined data did not show evidence for one fraction providing superior information over the other.

Funder

Movember Foundation

Prostate Cancer UK and Movember Foundation

The Masonic Charitable Foundation

the King family

Big C Cancer Charity

The Andy Ripley Memorial Fund

the Stephen Hargrave Trust

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference71 articles.

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2. National Institute for Health and Care Excellence (NICE) (2021). Prostate Cancer: Diagnosis and Management, National Institute for Health and Care Excellence (NICE).

3. Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer;Bernemann;Eur. Urol.,2017

4. Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer;Hennigan;JCO Precis. Oncol.,2019

5. Cancer Cells in Prostatic Secretions;Herbut;J. Urol.,1947

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