Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes
Open accessPublished version of a preprint
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.
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Cites
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- Authors
- Khoo, A., Govindarajan, M., Qiu, Z., Liu, L. Y., Ignatchenko, V., Waas, M., Macklin, A., Keszei, A., Neu, S., Main, B. P., Yang, L., Lance, R. S., Downes, M. R., Semmes, O. J., Vesprini, D., Liu, S. K., Nyalwidhe, J. O., Boutros, P. C., & Kislinger, T.
- Affiliations
- University Health Network (CA)
- University of California, Los Angeles (US)
- Sunnybrook Health Science Centre (CA)
- Eastern Virginia Medical School (US)
- University of Toronto (CA)
- Corresponding author
- Boutros, Paul C.
- Kislinger, Thomas
- ORCID
- Venue
- Nature Communications
- Published
- 2024-06-13
- Volume
- 15
- Issue
- 1
- Pages
- 5069-5069
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11176296
- OpenAlex
- W4399622071
- Cited by
- 40
- References
- 4
- Citations by year
- 2026: 18 · 2025: 18 · 2024: 4
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- PubMed Central (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (U01CA214194)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- prostate cancer, urinary proteome, extracellular vesicles, secreted proteins, urinary biomarkers, non-invasive diagnosis, risk stratification, longitudinal stability, benign prostatic lesions
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