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. ORCID:, Brewer, Daniel S. ORCID: 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

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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
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Depositing User: LivePure Connector
Date Deposited: 02 Feb 2023 16:30
Last Modified: 27 Feb 2023 10:31
DOI: 10.3390/cancers15030789

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