A recent study published on December 19, 2024, in the ExRNA journal highlights research from the Novosibirsk Institute of Chemical Biology and Fundamental Medicine, in collaboration with the E.N. Meshalkin National Medical Research Center. The researchers demonstrated that measuring microRNA levels in urinary extracellular vesicles serves as a promising biomarker for diagnosing and stratifying the prognosis of prostate cancer. This method can also evaluate the efficacy of treatments such as radiotherapy and monitors disease progression.
By enabling early diagnosis and detecting cancer relapse after treatment, this approach holds the potential to significantly enhance patient survival outcomes.
Recent statistics reveal that cancer continues to be one of the leading causes of death worldwide, with prostate cancer (PCa) ranking among the most common cancers in men. Effective management of PCa relies on timely primary diagnosis, optimized treatment strategies, and ongoing monitoring of treatment efficacy, along with early intervention to prevent metastasis. Radiotherapy remains the most widely used treatment for PCa; however, 30%–50% of patients undergoing radiotherapy experience biochemical recurrence (BCR), defined as a prostate-specific antigen (PSA) level of 0.2 ng/mL or higher, within 10 years post-treatment. Despite significant advancements in molecular biology and imaging technologies, the PSA blood test continues to serve as the gold standard for PCa screening, even though the U.S. Preventive Services Task Force has not recommended its use for prostate cancer diagnosis since 2012.
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The growing focus on personalized medicine has sparked the need for new diagnostic and prognostic markers, especially those based on molecular biology. To effectively monitor prostate cancer (PCa) treatment, methods must be affordable, reliable, and easily accessible, enabling ongoing health tracking both before and after therapy. Biological fluids, particularly blood and urine, provide the most accessible biomaterials for monitoring cancer progression in patients.
Extracellular vesicles (EVs), a class of membrane vesicles released by all cell types, have garnered significant attention for their role in intercellular communication. Once considered mere cellular waste, EVs are now recognized as key mediators of physiological processes and contributors to disease development. They transport various biomolecules, including lipids, RNA species (such as miRNAs, mRNAs, and long non-coding RNAs), oncoproteins, oncopeptides, and DNA fragments, from donor to recipient cells. Notably, MicroRNA (miRNAs) within EVs play critical roles in tumor growth, invasion, and metastasis, with their levels fluctuating not only between healthy individuals and cancer patients but also throughout disease progression and treatment.
“Changes in microRNA concentrations and ratios are observed during the development of many diseases, including oncological ones, such as prostate cancer. Ideally, as a patient is treated and recovering, all microRNA levels should tend toward healthy levels,” says Olga Bryzgunova co-author of the study who began the project and is currently a PhD at the Institute of Chemical Biology and Fundamental Medicine.
However, despite extensive research conducted in Russia and globally over many years, no single diagnostic or prognostic microRNA has been identified to reliably predict prostate cancer or assess the efficacy of cancer therapies. This challenge stems from the complex nature of microRNAs, which influence numerous critical genes in a network where a single gene can be regulated by multiple microRNAs, and a single microRNA can impact numerous genes.
The study investigates the expression levels of 14 microRNAs (miRNAs), arranged into 61 ratios, in urinary extracellular vesicles (EVs) from healthy males and prostate cancer (PCa) patients, tracking changes in miRNA dynamics before radiotherapy and at 1 and 3 months post-treatment. These miRNAs were selected based on prior research and their involvement in biological processes disrupted during prostate cancer progression. The analysis revealed significant differences in 42 miRNA ratios (out of 61 ratios studied) between healthy individuals and PCa patients, highlighting their diagnostic potential. Among these, 14 ratios demonstrated the highest sensitivity and specificity, with miRNA-30e/31 showing the strongest diagnostic performance. The primary aim of the study was to assess the impact of radiotherapy on these 14 miRNAs. Results showed that 43 miRNA ratios exhibited significant changes over the three-month timeline post-radiotherapy, with 19 ratios either returning to or shifting toward a normal profile compared to healthy donors. These findings underscore the potential of miRNA ratios for evaluating radiotherapy efficacy and for predicting and monitoring disease progression in prostate cancer patients.
The study sheds light on the intricate relationship between microRNA (miRNA) expression and radiotherapy, emphasizing the significant potential of miRNAs as biomarkers for assessing treatment response and tracking disease progression in prostate cancer. By unraveling how miRNA dynamics interact with therapeutic interventions, the research highlights their promising clinical utility. However, the complexity of miRNA expression patterns, influenced by various biological and environmental factors, poses challenges that warrant further investigation. Continued research is essential to clarify the precise roles of miRNAs in cancer development, treatment response, and resistance, particularly in understanding their long-term effects on patient outcomes, including relapse and metastasis. Such efforts could ultimately enable the development of more personalized and effective therapeutic strategies for prostate cancer management.
