Abstract

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome. For this purpose, two patient cohorts were enrolled, including OvCa cases who underwent a diagnostic or cytoreductive surgery, and non-oncological patients as controls, who underwent abdominal surgery for benign gynecological conditions. PFD-sEVs systematic extraction from surgical samples enabled us to observe significant quantitative and qualitative differences associated with cancer diagnosis, disease stage and platinum chemosensitivity. Proteomic profiling of PFD-sEVs led to the identification of molecular pathways and proteins of interest and to the biological validation of S100A4 and STX5. In addition, unsupervised analysis of PFD-sEVs proteomic profiles in high-grade serous ovarian carcinomas (HGSOC) revealed two clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of the PFD-sEVs content provided a prognostic value with potential implications in HGSOC clinical management.

Authors

Miguel Quiralte, Arantzazu Barquín, Mónica Yagüe Fernández, Paloma Navarro, Tatiana P. Grazioso, Elena Sevillano, Juan F. Rodriguez Moreno, Alejandra Balarezo-Saldivar, Héctor Peinado, Elena Izquierdo, Carlos Millán, Irene López Carrasco, Mario Prieto, Rodrigo Madurga de Lacalle, Ismael Fernández-Miranda, Sergio Ruiz-Llorente, Jesús García-Donas

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