Urinary extracellular vesicles – a diagnostic tool for prostate cancer

Urine, a common and easily obtainable biofluid, offers a wealth of information about our body’s overall health and the specific state of our genitourinary system. Recent research has led to greater understanding of the complexity and clinical utility of urine, particularly focusing on its potential in diagnosing prostate cancer.

The Complexity of Urine

Urine is not just a waste product; it carries a wide array of proteins that can tell us a lot about what’s happening inside our bodies. These proteins come in two main forms:

  1. Secreted Proteins: These are proteins released directly into the urine.
  2. Extracellular Vesicle (EV) Proteins: These are proteins encapsulated in tiny particles called extracellular vesicles, which are derived from the tissues the urine passes through.

By studying these proteins, scientists can get a detailed snapshot of the body’s physiological state and the health of the genitourinary tissues.

A Study on Urinary Proteomes

A comprehensive study by researchers at the University of Toronto involving 190 men, including some with prostate cancer, aimed to quantify and understand the proteins present in urine. The researchers used a straightforward method to enrich prostatic proteins (proteins from the prostate) in urine samples. Here are some key findings from the study:

  1. Different Origins of Proteins: The study found that secreted proteins and EV proteins come from different parts of the cell. This distinction is crucial because it affects how we interpret the presence and role of these proteins.
  2. Faithful Surrogates: Urinary EVs closely resemble the protein composition of the tissues they come from, making them reliable indicators of tissue health. In contrast, secreted proteins in urine or proteins from cell line EVs do not provide as accurate a reflection of tissue conditions.
  3. Stability Over Time: The urinary proteome (the complete set of proteins found in urine) remains stable over several years. This stability is essential for developing reliable diagnostic tests and biomarkers.
  4. Cancer Detection: The study demonstrated that the urinary proteome could distinguish between malignant (cancerous) and benign (non-cancerous) prostatic lesions. It also showed potential in risk stratifying prostate tumors, helping to identify how aggressive a tumor might be.

uEV proteome closely reflects the prostate tissue proteome

Fig. 3

a Overlap in proteins quantified in each sample type. Samples: Urinary soluble proteins (uSP) = 175, uEV-P150 = 148, uEV-P20 = 146, Tissue = 157; Proteins: uSP = 3150, uEV-P150 = 3878, uEV-P20 = 5462, Tissue = 7438. b log2 median protein abundance between prostate tissue and uSP (left), uEV-P20 (middle), and uEV-P150 (right). Spearman’s rank correlation and its P-value (two-tailed) are shown. c Analysis strategy to identify tissue-associated genes in RNA-seq of normal or normal adjacent to tumor (NAT) prostate, bladder, and kidney from the Genotype-Tissue Expression project (GTEx) or The Cancer Genome Atlas (TCGA). P-values from the two-sided Mann–Whitney U test adjusted using the Benjamini–Hochberg method (FDR). d Gene set variation analysis scores (GSVA) of sample types based on tissue-specific signatures (prostate: purple, kidney/bladder: grey). Samples: uSP = 175, uEV-P150 = 148, uEV-P20 = 146, Tissue = 157. P-values from two-sided Mann–Whitney U test. Boxplots are shown with the line indicating the sample median, the box indicating the 25th and 75th percentiles, and the whiskers indicating ±1.5 × IQR. e Gene Ontology: Cellular Component (GO:CC) gene sets over-represented in each sample type. Only significant gene sets (g:SCS-adjusted P-value < 0.05 from a Fisher’s one-tailed test in g:Profiler are visualized. Source data are provided as a Source Data file.

The Synergistic Value of Urinary Proteins

One of the most exciting aspects of this research is the combined value of secreted and EV proteins in urine. By analyzing both types of proteins, scientists can gain a more comprehensive understanding of the urinary proteome. This synergy enhances the potential for translational studies (applying findings from basic research to clinical settings) and biomarker development (identifying biological markers that indicate a disease state).

Implications for Prostate Cancer Diagnosis

Prostate cancer is one of the most common cancers among men, and early detection is crucial for effective treatment. The ability to non-invasively distinguish between malignant and benign prostatic lesions using urine samples is a significant advancement. It means that a simple urine test could help identify prostate cancer early, track its progression, and tailor treatments to individual patients more effectively.


This study underscores the immense potential of urine as a diagnostic tool, particularly in the context of prostate cancer. By harnessing the power of urinary proteomes—both secreted and EV proteins—researchers are paving the way for non-invasive, accurate, and reliable diagnostic tests. This approach not only enhances our understanding of urinary proteins but also holds promise for improving patient outcomes through better diagnosis and personalized treatment strategies. As research in this field continues to evolve, urine may become a key player in the future of personalized medicine and cancer diagnostics.

Khoo A, Govindarajan M, Qiu Z, Liu LY, Ignatchenko V, Waas M, Macklin A, Keszei A, Neu S, Main BP, Yang L, Lance RS, Downes MR, Semmes OJ, Vesprini D, Liu SK, Nyalwidhe JO, Boutros PC, Kislinger T. (2024) Prostate cancer reshapes the secreted and extracellular vesicle urinary proteomes. Nat Commun 15(1):5069. [article]

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