Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer

J Clin Invest. 2024 Apr 2;134(10):e176161. doi: 10.1172/JCI176161.

Abstract

Cancer-derived small extracellular vesicles (sEVs) are capable of modifying the 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, 2 patient cohorts were enrolled: patients with OvCa who underwent a diagnostic or cytoreductive surgery and nononcological patients, who underwent abdominal surgery for benign gynecological conditions and acted as the control group. Systematic extraction of PFD-sEVs 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-sEV proteomic profiles in high-grade serous ovarian carcinomas (HGSOCs) revealed 2 clusters with different outcomes in terms of overall survival. In conclusion, comprehensive characterization of PFD-sEV content provided a prognostic value with potential implications in HGSOC clinical management.

Keywords: Cancer; Obstetrics/gynecology; Oncology; Proteomics.

Publication types

  • Observational Study
  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Ascitic Fluid* / metabolism
  • Ascitic Fluid* / pathology
  • Extracellular Vesicles* / metabolism
  • Extracellular Vesicles* / pathology
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Prospective Studies
  • Proteomics*