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Purpose: Cancer statistics demonstrate leading growth of prostate cancer. As a rule, radical prostatectomy (RP) is a mandatory option in the treatment of localized prostate cancer (PCa). Over 30% of patients develop biochemical resistance after the surgery and over 30% of these patients experience prostate cancer recurrence and metastasis. Currently used PCa patient's diagnostic features fail to identify PCa recurrence. To identify the risk group of PCa patients after RP we attempt to apply miRNAs which were shown as promising liquid biopsy markers for PCa diagnosis and prognosis., Materials and Methods: Expression of 14 miRNAs closely involved in the development of prostate cancer from urine extracellular vesicles (uEV) of PCa patients before as well as 3, 6 and 12 months after radical prostatectomy was assessed using RT PCR and compared with their expression from uEV of healthy donors in the current study., Results: It was shown that 22 miRNA pairs prognostic ratios (MPPRs) significantly changed after radical prostatectomy. MPPRs the most promising in terms of evaluating the effectiveness of radical prostatectomy have been identified. These include two groups: MPPRs significantly changed after surgery towards that in healthy donors; and MPPRs, which divided PCa patients into two significantly different subgroups 3 or 6 months after radical prostatectomy., Conclusions: The obtained data indicate that urine EVs represent a valuable source of both MPDR and MPPR for prostate cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Radical prostatectomy, radiotherapy, chemotherapy, and androgen-deprivation therapy are among the most common treatment options for different forms of prostate cancer (PCa). However, making therapeutic decisions is difficult due to the lack of reliable prediction markers indicating therapy outcomes in clinical practice. The involvement of miRNAs in all mechanisms of the PCa development and their easy detection characterize them as attractive PCa biomarkers. Although there are extensive data on the role of miRNAs in PCa therapy resistance and sensitivity development, the issues of whether they could be used as a guide for therapy choice and, if so, how we can progress toward this goal, remain unclear. Thus, generalizable reviews and studies which summarize, compare, and analyze data on miRNA involvement in responses to different types of PCa therapies are required., Objectives: Data on the involvement of miRNAs in therapy responses, on the role of cross-miRNA expression in different therapies, and on miRNA targets were analyzed in order to determine the miRNA-related factors which can lend perspective to the future development of personalized predictors of PCa sensitivity/resistance to therapies., Materials and Methods: The data available on the miRNAs associated with different PCa therapies (resistance and sensitivity therapies) are summarized and analyzed in this study, including analyses using bioinformatics resources. Special attention was dedicated to the mechanisms of the development of therapy resistance., Results and Discussion: A comprehensive combined analysis of the current data revealed a panel of miRNAs that were shown to be most closely associated with the PCa therapy response and were found to regulate the genes involved in PCa development via cell proliferation regulation, epithelial-mesenchymal transition (EMT), apoptosis, cell-cycle progression, angiogenesis, metastasis and invasion regulation, androgen-independent development, and colony formation., Conclusion: The selected miRNA-based panel has the potential to be a guide for therapeutic decision making in the effective treatment of PCa., (© 2023 American Society of Andrology and European Academy of Andrology.)

Urine of prostate cancer (PCa) carries miRNAs originated from prostate cancer cells as a part of both nucleoprotein complexes and cell-secreted extracellular vesicles. The analysis of such miRNA-markers in urine can be a convenient option for PCa screening. The aims of this study were to reveal miRNA-markers of PCa in urine and design a robust and precise diagnostic test, based on miRNA expression analysis. The expression analysis of the 84 miRNAs in paired urine extracellular vesicles (EVs) and cell free urine supernatant samples from healthy donors, patients with benign and malignant prostate tumours was done using miRCURY LNA miRNA qPCR Panels (Exiqon, Denmark). Sets of miRNAs differentially expressed between the donor groups were found in urine EVs and urine supernatant. Diagnostically significant miRNAs were selected and algorithm of data analysis, based on expression data on 24-miRNA in urine and obtained using 17 analytical systems, was designed. The developed algorithm of data analysis describes a series of steps necessary to define cut-off values and sequentially analyze miRNA expression data according to the cut-offs to facilitate classification of subjects in case/control groups and allows to detect PCa patients with 97.5% accuracy., Competing Interests: The authors have declared that no competing interests exist.

Urine of prostate cancer patients contains tumor-specific biopolymers, including protein- and microvesiclesassociated miRNAs that can potentially be used as oncomarkers. Previously we have characterized urine extracellular vesicles and demonstrated diagnostic potential of their miRNA cargo. In this study, we have performed a comparative analysis of the expression of 84 miRNA in paired samples of urine microvesicles and clarified urine from healthy men, patients with benign hyperplasia and cancer of the prostate using miRCURY LNA miRNA qPCR Panels. Subsets of miRNAs with differences in expression between the fractions of the urine were found in all three groups. Two groups of miRNA were identified based on the patterns of their differential expression. They regulate several key signaling pathways associated with prostate cancer development.

The aim of our study was to attract the attention of researchers at the problem of contamination of exosome preparations. Using a transmission electron microscope JEM-1400 ("JEOL", Japan) we have examined exosome preparations, isolated according to the conventional scheme of sequential centrifugation from different biological fluids: plasma and urine of healthy persons and patients with oncologic diseases, bovine serum, and culture fluid (MDCK, MDA-MB и MCF-7 cells). All exosome preparations (over 200) contained exosomes, which were identified by immuno-electron microscopy using antibodies to tetraspanins CD63 or CD9. Besides exosomes, all the studied preparations contained contaminating structures: distinct particles of low electron density without limiting membrane ("non-vesicles"). Two main kinds of the "non-vesicles" species were found in exosome preparations: 20-40 nm in size, representing 10-40% of all structures in the preparations; and 40-100 nm in size (identical to exosomes by size). Morphology of the "non-vesicles" allowed to identify them as lipoproteins of intermediate and low density (20-40 nm), and very low density (40-100 nm). The highest level of the contamination was detected in exosome preparations, isolated from blood samples. The results of our study indicate the need to control the composition of exosome preparation by electron microscopy and take into account the presence of contaminating structures in analysis of experimental data.

Epigenetic differences are a common feature of many diseases, including cancer, and disease-associated changes have even been detected in bodily fluids. DNA modification studies in circulating DNA (cirDNA) may lead to the development of specific non-invasive biomarkers. To test this hypothesis, we investigated cirDNA modifications in prostate cancer patients with locally confined disease (n = 19), in patients with benign prostate hyperplasias (n = 20) and in men without any known prostate disease (n = 20). This initial discovery screen identified 39 disease-associated changes in cirDNA modification, and seven of these were validated using the sodium bisulfite-based mapping of modified cytosines in both the discovery cohort and an independent 38-patient validation cohort. In particular, we showed that the DNA modification of regions adjacent to the gene encoding ring finger protein 219 distinguished prostate cancer from benign hyperplasias with good sensitivity (61%) and specificity (71%). We also showed that repetitive sequences detected in this study were meaningful, as they indicated a highly statistically significant loss of DNA at the pericentromeric region of chromosome 10 in prostate cancer patients (p = 1.8 × 10(-6)). Based on these strong univariate results, we applied machine-learning techniques to develop a multi-locus biomarker that correctly distinguished prostate cancer samples from unaffected controls with 72% accuracy. Lastly, we used systems biology techniques to integrate our data with publicly available DNA modification and transcriptomic data from primary prostate tumors, thereby prioritizing genes for further studies. These data suggest that cirDNA epigenomics are promising source for non-invasive biomarkers.

The review highlights analytics capacities of immunochemical and molecular-genetic methods used in the non-invasive test for prostate cancer and monitoring of efficacy of anticancer therapy. The perspectives of their applications in clinical practice also have been evaluated.