Gene-transcript expression in urine supernatant and urine cell-sediment are different but equally useful for detecting prostate cancer

Yazbek Hanna, Marcelino, Winterbone, Mark, O'Connell, Shea P., Olivan, Mireia, Hurst, Rachel, Mills, Rob, Cooper, Colin S., Brewer, Daniel S. and Clark, Jeremy (2023) Gene-transcript expression in urine supernatant and urine cell-sediment are different but equally useful for detecting prostate cancer. Cancers, 15 (3). ISSN 2072-6694

Preview

PDF (2023_Yazbek Hanna et al_Cancers) - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

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 ~20x 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.

Item Type:	Article
Additional Information:	Funding: This study was possible thanks to the Movember Foundation (GAP1) Urine Biomarker project, a Prostate Cancer UK and Movember Foundation Research Innovation Award (RIA18-ST2-014), The Masonic Charitable Foundation, The Bob Champion Cancer Trust, the King family, Big C Cancer Charity, The Andy Ripley Memorial Fund and the Stephen Hargrave Trust. The sponsors had no role in the design, execution, interpretation, or writing of the study.
Uncontrolled Keywords:	biomarker,cancer,cell-sediment,extracellular vesicles,prostate,urine,oncology,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	02 Feb 2023 16:30
Last Modified:	06 Feb 2025 11:16
URI:	https://ueaeprints.uea.ac.uk/id/eprint/90941
DOI:	10.3390/cancers15030789

Downloads

Actions (login required)

View Item