Cancer is the second most common cause of death in both men and women globally. In 2020, 1.41 million people were diagnosed with prostate cancer worldwide.1 With over 300,000 deaths caused by prostate cancer in 2022, early identification is critical for lowering mortality.2
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Exosomal RNA has recently received significant attention as a potential biomarker for the early identification of cancers. This includes liver, breast, and prostate cancer.3,4
The prostate is a small, walnut-shaped gland beneath the bladder and in front of the rectum. It produces seminal fluid, which transports sperm.
What causes prostate cancer?
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Prostate cancer is classified into several types, with adenocarcinoma being the most common. Other types include small cell carcinoma, sarcoma, neuroendocrine tumors, and transitional cell carcinoma.
In its early stages, prostate cancer often progresses slowly and remains localized within the prostate.5 This makes early detection more difficult. However, if identified early, the cancer is highly treatable and can often be eradicated.
This article will discuss the symptoms and risk factors of prostate cancer, as well as current screening methods. It will also highlight the significance of exosomal mRNA and present two studies exploring the potential of exosomal mRNAs as a non-invasive biomarker for early prostate cancer screening.
Prostate cancer risk factors
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Because prostate cancer grows slowly, there may be no signs or symptoms in its early stages. However, some symptoms may appear in the later stages of cancer progression.
These can include difficulty urinating, increased urgency and frequency of urination, blood in the urine, blood in the semen, bone pain, decreased force of urine flow, erectile dysfunction, and weight loss.
Like many other cancers, the exact cause of prostate cancer remains unclear. However, several risk factors have been identified. These include age (50 years or older), family history (a history of prostate cancer), and weight (obesity), all of which have been linked to an increased risk of developing the disease.6
Race is also associated with a higher risk of prostate cancer. A 2023 study found that black men have a greater risk of developing prostate cancer compared to non-Hispanic white men. This may be due to genetic factors, dietary differences, or increased levels of stress.7
Screening methods for prostate cancer
The most common approach to diagnosing prostate cancer, according to the Centers for Disease Control and Prevention (CDC), is through biopsy.8 A prostate biopsy is a procedure that removes a small sample of prostate tissue for further investigation.
A needle is inserted into the prostate to collect multiple samples of suspicious tissue. This method of diagnosis is highly invasive, painful, and uncomfortable.
Before a prostate biopsy is performed, various preliminary screening procedures are typically conducted. These include a digital rectal exam (DRE), a blood test for prostate-specific antigen (PSA), a transrectal ultrasound, and magnetic resonance imaging (MRI).9
The PSA blood test is the most commonly used method for prostate cancer screening. This test measures the level of prostate-specific antigen (a protein) in the body. Individuals with prostate cancer tend to have increased PSA levels.
Although PSA blood tests are widely used, they can be unreliable because there are several other reasons why PSA levels may be elevated.
Normal prostate cells also produce PSA, so benign (non-cancerous) conditions such as prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH), or an enlarged prostate, can raise PSA levels in the bloodstream.10 Strenuous exercise, ejaculation, or even a car accident could also increase PSA levels.
The unreliability of PSA blood tests and the invasive nature of biopsies highlight the need for a more dependable, non-invasive method of prostate cancer screening.
Exosomal mRNAs have recently gained attention from researchers as a potential biomarker for prostate cancer detection. Sample collection for exosomal mRNA is significantly less invasive, as exosomes are present in body fluids.
Moreover, the specificity of exosomal mRNAs may allow for more accurate and reliable results compared to PSA blood tests.
Understanding mRNA and exosomes
What is mRNA?
Messenger RNA (mRNA) is a single-stranded molecule involved in protein synthesis. mRNAs are transcribed from a DNA template and carry protein-coding information from the cell’s nucleus to the cytoplasm.11
mRNA research offers vital insights into gene expression, cellular function, and specific mutations associated with diseases such as cancer.
What are exosomes?
Exosomes are extracellular vesicles (EVs) released by various cell types. They are found in physiological fluids such as plasma, urine, and saliva. These vesicles are enclosed by a lipid bilayer and carry a wide range of biomolecules, including nucleic acids and proteins, both inside and on their surface.
Exosomes play essential roles in cell-to-cell communication, cellular maintenance, and tumor progression.12 They transport information from all cells, both healthy and diseased, making them valuable for understanding disease mechanisms and developing diagnostics or therapies.
Biomarkers for cancer
Circulating exosomal mRNA
A 2021 study analyzed circulating exosomal mRNA to investigate its potential as a biomarker for prostate cancer. Exosomes can be found throughout the body and may carry different information depending on their location.
To demonstrate that exosomal mRNAs can produce results as accurate as those from cancerous prostate tissue, the researchers used RNA sequencing to compare tissue-derived mRNA with circulating exosomal mRNA from blood samples.
They found that both mRNA from prostate cancer tissue and circulating exosomal mRNA contained the same information. Samples were collected from 76 prostate cancer patients and 84 individuals with BPH.
After a series of RNA sequencing analyses, the researchers identified six circulating exosomal mRNAs with significantly different expression levels among prostate cancer patients, BPH patients, and a control group.13
These findings showed strong potential for using circulating exosomal mRNA as a biomarker to detect prostate cancer. Blood samples were used in this study because exosomes can be detected in both blood and plasma.
However, this method is not entirely noninvasive. Is there a truly noninvasive way to detect prostate cancer? Yes—a recent 2024 study explored the use of urinary exosomal mRNA for this purpose.
Urinary exosomes mRNA
Jiayin Yu et al. studied the use of urinary exosomal mRNAs as a potential biomarker for the early detection of prostate cancer.
They selected urine because it allows for easy, noninvasive sample collection, making it suitable for large-scale screening and early detection.
Exosomal mRNA was chosen due to its stability in the body. The lipid bilayer of exosomes protects the genetic material inside from degradation by nucleases.
Next-generation sequencing of urinary exosomal RNA
Key mRNA biomarkers identified for prostate cancer screening
The study revealed: “The top ten mRNAs showing the most significant differences associated with prostate cancer were chosen as candidate genes. These genes were RAB5B, WWP1, MCF2L, HIST2H2BF, ZFY, MARK2, PASK, RBM10, NRSN2, and PCGF1."
Subsequent qPCR and electrophoresis analysis showed that eight of these mRNAs (RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2) outperformed blood PSA as indicators of prostate cancer.
The study concluded that their comprehensive model using urinary exosomal mRNAs outperformed existing PSA screening methods, with a sensitivity of 70–90 % and specificity of 20–40 %.14
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Summary
Prostate cancer remains a leading cause of death among men. Although several screening methods exist, such as digital rectal exams (DRE) and blood PSA tests, they can be invasive and often lack reliability.
This highlights the need for a non-invasive, more accurate, and reliable method for detecting prostate cancer.
Current research on urinary exosomal mRNA shows promising potential for early diagnosis. However, further studies are needed to establish urinary exosomal mRNAs as a reliable diagnostic tool for prostate cancer.
With that in mind, Norgen Biotek is committed to supporting continued research through its urine exosome kits, including the Urine Exosome RNA Isolation Kit and the Urine Exosome Purification and RNA Isolation Kit.
References and further reading
- World Health Organization (2025). Cancer. (online) World Health Organization. Available at: https://www.who.int/news-room/fact-sheets/detail/cancer.
- World Cancer Research Fund International (2020). Prostate cancer statistics | world cancer research fund international. (online) WCRF International. Available at: https://www.wcrf.org/cancer-trends/prostate-cancer-statistics/.
- Jia, Y., et al. (2017). Exosome: emerging biomarker in breast cancer. Oncotarget, (online) 8(25), pp.41717–41733. https://doi.org/10.18632/oncotarget.16684.
- Li, Y., et al. (2015). Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Research, 25(8), pp.981–984. https://doi.org/10.1038/cr.2015.82.
- Cleveland Clinic (2023). Prostate Cancer: Symptoms, Diagnosis & Treatment. (online) Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/diseases/8634-prostate-cancer.
- Lee, S. (2020). Risks for prostate cancer. (online) Canadian Cancer Society. Available at: https://cancer.ca/en/cancer-information/cancer-types/prostate/risks.
- Vickers, A. J., Mahal, B., and Ogunwobi, O. O. (2023, January). Racism does not cause prostate cancer, it. ASCO Publications.
- CDC (2024). Diagnosing Prostate Cancer. (online) Prostate Cancer. Available at: https://www.cdc.gov/prostate-cancer/diagnosis/index.html.
- Mayo Clinic (2019). Prostate biopsy - Mayo Clinic. (online). Available at: https://www.mayoclinic.org/tests-procedures/prostate-biopsy/about/pac-20384734.
- National Cancer Institute (2022). Prostate-Specific Antigen (PSA) Test. (online) National Cancer Institute. Available at: https://www.cancer.gov/types/prostate/psa-fact-sheet.
- Sen, S. (2024). Messenger RNA (mRNA). (online) Genome.gov. Available at: https://www.genome.gov/genetics-glossary/messenger-rna.
- Doyle, L. and Wang, M. (2019). Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells, (online) 8(7), p.727. https://doi.org/10.3390/cells8070727.
- Ji, J., et al. (2021). Circulating exosomal mRNA profiling identifies novel signatures for the detection of prostate cancer. Molecular Cancer, 20(1). https://doi.org/10.1186/s12943-021-01349-z.
- Yu, J., et al. (2024). Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis. BMC Urology, 24(1). https://doi.org/10.1186/s12894-024-01540-6.
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