4.4 Article

Analysis of EVs from patients with advanced pancreatic cancer identifies antigens and miRNAs with predictive value

Journal

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
Volume 29, Issue -, Pages 473-482

Publisher

CELL PRESS
DOI: 10.1016/j.omtm.2023.05.009

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In this study, blood-derived extracellular vesicles (EVs) from patients with advanced pancreatic cancer were analyzed to identify molecular signatures predictive of therapy response. The EV concentration and size did not differ significantly between responders and non-responders, but there was decreased expression of SSEA4 and CD81 in responder patients. Analysis of EV miRNAs revealed at least 44 differentially expressed miRNAs between responders and non-responders. These findings demonstrate the potential of EV-derived biomarkers in predicting therapy response in pancreatic cancer.
The identification of predictive factors for treatment of pancreatic cancer (PC) is an unmet clinical need. In the present work, we analyzed blood-derived extracellular vesicles (EVs) from patients with advanced PC in order to find a molecular signature predictive of response to therapy. We analyzed samples from 21 patients with advanced PC, all receiving first-line treatment with gemcitabine + nab-paclitaxel. Isolated EVs have been analyzed, and the results of laboratory have been matched with clinical data in order to investigate possible predictive factors. EV concentration and size were similar between responder and non-responder patients. Analysis of 37 EV surface epitopes showed a decreased expression of SSEA4 and CD81 in responder patients. We detected more than 450 expressed miRNAs in EVs. A comparative survey between responder and non responder patients showed that at least 44 miRNAs were differently expressed. Some of these miRNAs have already been observed in relation to the survival and gemcitabine sensitivity of tumor cells. In conclusion, we showed the ability of our approach to identify EV-derived biomarkers with predictive value for therapy response in PC. Our findings are worthy of further investigation, including the analysis of samples from patients treated with different schedules and in different settings.

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