Multi-omics Analysis of Prostate Derived Extracellular Vesicles: an Observational Retrospective Study for Prostate Cancer Diagnosis and Monitoring

Overview

Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Over 1.4 million new cases of prostate cancer are estimated to occur worldwide each year, with more than 375,000 related deaths. High-risk PCa poses significant challenges due to the aggressive nature of the disease and the ability to create an immunosuppressive tumor microenvironment (TME), thereby hampering the effectiveness of existing therapies. Despite advances in diagnostics and treatment, the mechanisms driving immune evasion and tumor progression in high-risk PCa remain poorly understood. These considerations underscore the urgent need for innovative strategies to address these challenges and improve patient outcomes. Extracellular vesicles (EVs) have emerged as critical players in cancer biology. EVs carry molecular cargo, including proteins, RNA, lipids, and metabolites, enabling mediation of intercellular communication and influence on cancer progression. Tumor-derived EVs (TDEVs) are particularly implicated in promoting tumor growth, reprogramming the TME, and suppressing antitumor immune responses. Owing to the intrinsic ability to mediate intercellular communication and transport biomolecules to distant sites, EVs represent key contributors to cancer pathogenesis. A previous study demonstrated, through comprehensive metabolomics profiling, a combination of small molecules extracted from expressed prostatic secretion (EPS)-urine, integrated with clinical parameters, that could effectively identify and stratify PCa patients, highlighting the potential of this biofluid in PCa diagnostics. EPS-urine represents a unique biofluid enriched with EVs secreted directly by prostate tissue, offering a valuable source for the study of prostate-specific EVs. Based on this evidence, the potential of prostate cancer (PCa)-derived EVs is being explored as a transformative approach for the management of high-risk prostate cancer. The project qualifies as a basic research study with potential translational relevance. An observational retrospective study has been designed with the objective of comprehensively characterizing extracellular vesicles (EVs) derived from EPS-urine using multi-omics approaches. The analysis will be conducted on samples from 100 patients, all recruited exclusively at the Department of Urology at IRCCS San Raffaele Hospital. Patients are categorized into two groups: patients with clinically significant prostate cancer (csPCa), including intermediate-risk PCa (ISUP grade 2-3) and high-risk PCa (ISUP grade 4-5), and patients with non-clinically significant PCa (non-csPCa), including low-risk PCa (ISUP grade 1) and patients with benign prostatic hypertrophy. The study is expected to provide unprecedented insights into prostate tissue-derived EVs, laying the foundation for functional validation of key molecular markers and pathways implicated in PCa progression.