Urine as an emerging liquid biopsy for prostate cancer biomarker detection
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Urine: a promising sample type to detect and monitor prostate cancer
Finding new and specific biomarkers for prostate cancer can improve cancer detection and overall patient outcomes.
The increasing knowledge of multi-omics has great potential for prostate cancer research. Several biomarker candidates have been identified in urine. Urine, as a non-invasive liquid biopsy sample type, offers new ways to screen for this cancer (1,2) and presents advantages over current testing methods as the process is easy, quick, and non-invasive.
Current methods for prostate cancer detection have limitations
The most commonly used tests for prostate cancer detection are the prostate-specific antigen (PSA) blood test, an MRI, and/or a biopsy (3). Non-cancerous conditions can also result in elevated serum PSA levels, resulting in poor specificity. Additionally, biopsies can be painful, invasive, difficult to perform, and have associated complications (1).
Another challenge with current prostate cancer detection methods is the inability to differentiate aggressive tumors from slow-growing ones. Many types of prostate cancer tumors are slow-growing and may not require treatment in a man’s lifetime. Therefore, it is important to establish the severity of the cancer in order to prevent overdiagnosis and overtreatment (3).
Urine as a sample type
Studies have shown that there are various biomarker candidates for prostate cancer that are found in urine, including prostate cells, DNA, RNA, proteins, extracellular vesicles, including exosomes and other small molecules (1).
Epigenomics - DNA methylation markers are attractive for prostate cancer
The most common (>90%) genetic alteration reported to date in prostate cancer is the epigenetic silencing of the glutathione-S transferase P1 (GSTP1) gene, as a result of promotor hypermethylation (1). Other epigenetic alterations are also being investigated as biomarkers for prostate cancer detection. DNA methylation is particularly interesting as the alterations remain stable in body fluids, such as urine, and occur in well-defined regions, making it easier to detect by sensitive PCR-based assays (1).
Transcriptomics - miRNAs are exciting in cancer detection
The most common RNA-based urinary marker for prostate cancer is Prostate Cancer Antigen 3 (PCA3), a prostate-specific long noncoding mRNA. The PCA3 gene is overexpressed in 95% of all primary prostate cancer cases and absent in benign prostate tissue and other tumor types, making it a relatively specific biomarker for the type of cancer (1). Another highly specific RNA-based urinary biomarker for prostate cancer is the TMPRSS2-ERG (transmembrane protease, serine 2 – E26 transformation specific (ETS) related oncogene (ERG) fusion gene (1).
Commercially available urine tests for prostate cancer are on the market using both PCA3 and TMPRSS2-ERG. While miRNAs are very stable and detectable in body fluids, such as urine, more studies are required to further investigate the connection between RNA biomarkers and prostate cancer.
To date, four urinary tests for prostate cancer are commercially available:
Ongoing research & future perspectives
Many proteins have been suggested as candidate biomarkers; however, to date, no protein biomarkers have entered clinical use for prostate cancer (1). Additional studies must be performed to better understand the potential and accuracy of proteins as a diagnostic biomarker in urine for prostate cancer testing. Recent research by the University of East Anglia has shown that a prostate cancer-urine test can help identify prostate cancer tumors.
The Prostate Urine Risk (PUR) test, which looks for certain biomarkers in urine could identify men with high, intermediate, or low risk for prostate cancer (3). Further development of the test can now help determine disease aggressiveness. The model named ExoGrail combines the measurement of a protein-marker called EN2 and 10 other genes measured in urine. This approach can help direct treatment options, by suggesting which patients need to undergo treatment immediately and those who can be transferred to active surveillance. Further validation of this research will be conducted in a larger study cohort, but the current findings are promising for urinary prostate cancer research (3,4,5).
Importantly, to use urine for clinical applications, the collection, transport, and storage of urine should be optimized. Additionally, first-void urine (first 20 – 30 mL of urine) has shown to be valuable for prostate cancer detection, highlighting the potential need to accurately collect this fraction (1).
Our urine collection device, Colli-Pee®, allows for volumetric and standardized collection of first-void urine. The device’s design enables immediate mixing with a preservative, improving sample stability. Colli-Pee® is available neat and prefilled with the stabilizer UCM, allowing the preservation of DNA in urine, some variants are CE-IVD marked, and registered in several countries outside of Europe.
Novosanis is actively investigating urine for prostate cancer research – read more about our ongoing project, titled Urine as a Liquid Biopsy for Cancer Detection (URODETECT), which focusses on the two common cancer types in men and women, prostate and breast cancer respectively.
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Mehta et. al, Novosanis White Paper - Urine as a sample type for multi-omic cancer research, June 2021
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https://www.uea.ac.uk/news/-/article/prostate-cancer-urine-test-identifi...
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Connell SP, Mills R, Pandha H, Morgan R, Cooper CS, Clark J, Brewer DS, The Movember Gap Urine Biomarker Consortium. Integration of Urinary EN2 Protein & Cell-Free RNA Data in the Development of a Multivariable Risk Model for the Detection of Prostate Cancer Prior to Biopsy. Cancers (Basel). 2021 Apr 27;13(9):2102. doi: 10.3390/cancers13092102. PMID: 33925381; PMCID: PMC8123800.
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Clark, J., Hurst, R., Winterbone, M. S., Pandha, H., Perry, A., McGrath, S., Morgan, R., Connor, A. E., Jordan, A. C., Winrow, D., & Cooper, C. (2021). Urine Biomarkers for Prostate Cancer Diagnosis and Progression. Société Internationale d’Urologie Journal, 2(3), 159-170. https://doi.org/10.48083/SAWC9585