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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.)

The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539, also known as FAM214B) in the total pool of blood cell-free DNA, including cell-free DNA from plasma and cell-surface-bound DNA, of patients with prostate cancer and healthy donors was studied on the MiSeq platform. Our study found a higher methylation index of loci for total cell-free DNA compared with cell-free DNA. For total cell-free DNA, the methylation of GSTP1 in each of the 11 positions provided a complete separation of cancer patients from healthy donors, whereas for cell-free DNA, there were no positions in the three genes allowing for such separation. Among the prostate cancer patients, the minimum proportion of GSTP1 genes methylated in any of the 17 positions was 12.1% of the total circulated DNA fragments, and the minimum proportion of GSTP1 genes methylated in any of the 11 diagnostically specific positions was 8.4%. Total cell-free DNA was shown to be more convenient and informative as a source of methylated DNA molecules circulating in the blood than cell-free DNA.

The locus-specific methylation of three genes (GSTP1, RNF219, and KIAA1539 (also known as FAM214B)) in the blood plasma cell-free DNA (cfDNA) of 20 patients with prostate cancer (PCa), 18 healthy donors (HDs), and 17 patients with benign prostatic hyperplasia (BPH) was studied via the MiSeq platform. The methylation status of two CpGs within the same loci were used as the diagnostic feature for discriminating the patient groups. Many variables had good diagnostic characteristics, e.g., each of the variables GSTP1.C3.C9, GSTP1.C9, and GSTP1.C9.T17 demonstrated an 80% sensitivity at a 100% specificity for PCa patients vs. the others comparison. The analysis of RNF219 gene loci methylation allowed discriminating BPH patients with absolute sensitivity and specificity. The data on the methylation of the genes GSTP1 and RNF219 allowed discriminating PCa patients, as well as HDs, with absolute sensitivity and specificity. Thus, the data on the locus-specific methylation of cfDNA (with single-molecule resolution) combined with a diagnostic approach considering the simultaneous methylation of several CpGs in one locus enabled the discrimination of HD, BPH, and PCa patients.