细胞外小泡
卵巢癌
细胞外
癌症研究
医学
肿瘤科
结果(博弈论)
癌症
内科学
生物
病理
细胞生物学
数学
数理经济学
作者
Miguel Quiralte Pulido,Arantzazu Barquín,Mónica Yagüe Fernández,Paloma Navarro,Tatiana P. Grazioso,Elena Sevillano,Juan Francisco Rodríguez Moreno,Alejandra Balarezo-Saldivar,Héctor Peinado,Elena Izquierdo,Carmen Millán,I. López Carrasco,Mario Prieto,Rodrigo Madurga,Ismael Fernández‐Miranda,Sergio Ruiz‐Llorente,Jesús García-Donás
摘要
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.
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