Abstract
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.
Highlights
Prostate cancer (PCa) is still the second cause of cancer-related male deaths in highly developed countries [1]
A significant fraction of PCa patients arrives at diagnosis with advanced forms, while others retain indolent tumors which will never progress into aggressive stages [2, 3]
Different from other vesicles, which are generated by random shedding mechanisms or from dying cells by discharge, exosomes drive intra- and inter-tissue cross-talk [16,17,18], are involved in physiological tissue homeostasis and immune system regulation [11] and in processes [12, 19, 20] that are often aberrant in tumors [7]
Summary
Prostate cancer (PCa) is still the second cause of cancer-related male deaths in highly developed countries [1]. Different from other vesicles, which are generated by random shedding mechanisms or from dying cells by discharge, exosomes drive intra- and inter-tissue cross-talk [16,17,18], are involved in physiological tissue homeostasis and immune system regulation [11] and in processes [12, 19, 20] that are often aberrant in tumors [7] In this regard, PCa is characterized by multiple genomic lesions [21] and several variants seem to be associated with tumor development [22, 23]. In advocate for the use of new, non-invasive cancer monitoring line with the expression of its total content counterpart, RPPA tools in the personalized treatment of PCa. levels of phosphorylated EGFR (EGFR_pY1068) positively correlated with the fraction of A431 in mixed A431/CAFs EVs (Fig. S2F)
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