Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes

Amanda Khoo, Meinusha Govindarajan, Zhuyu Qiu, Lydia Y. Liu, Vladimir Ignatchenko, Matthew Waas, Andrew Macklin, Alexander Keszei, Sarah Neu, Brian P. Main, Lifang Yang, Raymond S. Lance, Michelle R. Downes, O. John Semmes, Danny Vesprini, Stanley K. Liu, Julius O. Nyalwidhe, Paul C. Boutros () and Thomas Kislinger ()
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Amanda Khoo: University of Toronto
Meinusha Govindarajan: University of Toronto
Zhuyu Qiu: University of California, Los Angeles
Lydia Y. Liu: University of Toronto
Vladimir Ignatchenko: University Health Network
Matthew Waas: University Health Network
Andrew Macklin: University Health Network
Alexander Keszei: University Health Network
Sarah Neu: Sunnybrook Health Sciences Centre
Brian P. Main: Eastern Virginia Medical School
Lifang Yang: Eastern Virginia Medical School
Raymond S. Lance: Spokane Urology
Michelle R. Downes: Sunnybrook Health Sciences Centre
O. John Semmes: Eastern Virginia Medical School
Danny Vesprini: University of Toronto
Stanley K. Liu: University of Toronto
Julius O. Nyalwidhe: Eastern Virginia Medical School
Paul C. Boutros: University of Toronto
Thomas Kislinger: University of Toronto

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Urine is a complex biofluid that reflects both overall physiologic state and the state of the genitourinary tissues through which it passes. It contains both secreted proteins and proteins encapsulated in tissue-derived extracellular vesicles (EVs). To understand the population variability and clinical utility of urine, we quantified the secreted and EV proteomes from 190 men, including a subset with prostate cancer. We demonstrate that a simple protocol enriches prostatic proteins in urine. Secreted and EV proteins arise from different subcellular compartments. Urinary EVs are faithful surrogates of tissue proteomes, but secreted proteins in urine or cell line EVs are not. The urinary proteome is longitudinally stable over several years. It can accurately and non-invasively distinguish malignant from benign prostatic lesions and can risk-stratify prostate tumors. This resource quantifies the complexity of the urinary proteome and reveals the synergistic value of secreted and EV proteomes for translational and biomarker studies.

Date: 2024
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DOI: 10.1038/s41467-024-49424-5

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