Proteomic profiles of peritoneal fluid-derived small extracellular vesicles correlate with patient outcome in ovarian cancer
Miguel Quiralte, … , Sergio Ruiz-Llorente, Jesús García-Donas
Miguel Quiralte, … , Sergio Ruiz-Llorente, Jesús García-Donas
Published April 2, 2024
Citation Information: J Clin Invest. 2024;134(10):e176161. https://doi.org/10.1172/JCI176161.
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Research Article Oncology

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

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.

Authors

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

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Figure 1

Characterization of PFD-sEVs in controls and patients with OvCa.

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Characterization of PFD-sEVs in controls and patients with OvCa. (A) Rep...
(A) Representative image of particle size distribution determined by NTA in control and OvCa patient samples. (B) Primary peak size of particles measured by NTA in control (n = 29) and OvCa patient samples (n = 74). (C) EV morphology observed by transmission electron microscopy in controls (n = 2) and patients with OvCa (n = 2). Scale bars: 200 nm. (D) Concentration analysis of all particles in control (n = 29) and OvCa patient samples (n = 74). (E) Analysis of PFD-sEV concentration in control (n = 29) and OvCa patient samples (n = 74). (F) Analysis of PFD-sEV concentration in control (CT, n = 29) and OvCa patient samples (n = 74) separated according to tumor stage (S) (stage I–II, n = 7; stage III–IV, n = 67). Additional information regarding histology is provided (HGSOC, high-grade serous ovarian carcinomas; LGSOC, low-grade serous ovarian carcinomas). (G) Analysis of PFD-sEV concentration in control (n = 29) and HGSOC patient samples according to surgical origin of samples (PRIM, primary/diagnostic [n = 25]; INT, interval [n = 24]; REL, relapse [n = 14]). (H) PFD-sEV concentration at different time points from HGSOC cases with serial samples (n = 8). (I) PFD-sEV concentration according to cisplatin sensitivity (SENSIT, sensitive [n = 35]; RESIST, resistant [n = 16]) in HGSOC cases. (J) PFD-sEV concentration in HGSOC cases according to BRCA status (WT, wild type [n = 36]; ALT, altered [n = 17]) or HRD status (HRP, homologous recombination proficient [n = 23]; HRD, homologous recombination deficient [n = 30]). Unless otherwise indicated, data are shown as median and IQR from each independent sample/experiment. *P < 0.05, **P < 0.01, Mann-Whitney test (B, D, E, I, and J) or Kruskal-Wallis test with Dunn’s multiple-comparison test and Bonferroni’s adjusted P values (F and G).