Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-β5, Survivin, TGF-β, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.
【저자키워드】 Protein-protein interaction networks, Tumour biomarkers, 【초록키워드】 Biomarker, feasibility, Cancer, Diagnosis, Antigen, PD-L1, Protein, Cohort, sera, Patient, pathway, Retrospective analysis, survivin, Follow-up, prognostic, information, patients, proteomic, marker, TGF-β, Signaling, Analysis, Predictive, Endpoint, profile, clinical setting, molecular test, EVs, biological fluid, men, Vesicle, approach, robust, IMPROVE, addition, clinically, applied, activated, differentially expressed, translational, diagnostic procedure, ERG, 【제목키워드】 Prostate cancer, extracellular vesicle, prognostic, proteomic,