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Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes

Author

Listed:
  • Amanda Khoo

    (University of Toronto
    University Health Network)

  • Meinusha Govindarajan

    (University of Toronto
    University Health Network)

  • Zhuyu Qiu

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

  • Lydia Y. Liu

    (University of Toronto
    University Health Network
    University of California, Los Angeles
    University of California, Los Angeles)

  • 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
    Eastern Virginia Medical School)

  • Raymond S. Lance

    (Spokane Urology)

  • Michelle R. Downes

    (Sunnybrook Health Sciences Centre
    University of Toronto)

  • O. John Semmes

    (Eastern Virginia Medical School
    Eastern Virginia Medical School)

  • Danny Vesprini

    (University of Toronto
    Sunnybrook Research Institute)

  • Stanley K. Liu

    (University of Toronto
    University of Toronto
    Sunnybrook Research Institute)

  • Julius O. Nyalwidhe

    (Eastern Virginia Medical School
    Eastern Virginia Medical School)

  • Paul C. Boutros

    (University of Toronto
    University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

  • Thomas Kislinger

    (University of Toronto
    University Health Network)

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.

Suggested Citation

  • 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 & , 2024. "Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49424-5
    DOI: 10.1038/s41467-024-49424-5
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    References listed on IDEAS

    as
    1. Michael Fraser & Veronica Y. Sabelnykova & Takafumi N. Yamaguchi & Lawrence E. Heisler & Julie Livingstone & Vincent Huang & Yu-Jia Shiah & Fouad Yousif & Xihui Lin & Andre P. Masella & Natalie S. Fox, 2017. "Genomic hallmarks of localized, non-indolent prostate cancer," Nature, Nature, vol. 541(7637), pages 359-364, January.
    2. Yunee Kim & Jouhyun Jeon & Salvador Mejia & Cindy Q Yao & Vladimir Ignatchenko & Julius O Nyalwidhe & Anthony O Gramolini & Raymond S Lance & Dean A Troyer & Richard R Drake & Paul C Boutros & O. John, 2016. "Targeted proteomics identifies liquid-biopsy signatures for extracapsular prostate cancer," Nature Communications, Nature, vol. 7(1), pages 1-10, September.
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