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 6

Volcano plots depicting differentially deregulated proteins in comparisons of interest.

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Volcano plots depicting differentially deregulated proteins in compariso...
(A) HGSOC versus controls (deregulated proteins [DEPs] = 96). (B) Cisplatin-resistant versus -sensitive patients (DEPs = 22). (C) BRCA-altered vs. WT (DEPs = 21). (D) Recurrence versus primary (DEPs = 181). Each graph depicts normalized z scores for each detected master protein versus their corresponding adjusted P values. Dashed lines represent adjusted P value thresholds lower than 0.01 or 0.05 (x axis) or fold changes (FCs) greater than 2 or less than –2 (y axis). Significantly deregulated proteins shown in the upper right quadrant (orange circles) denote proteins overrepresented in the group under study, while proteins labeled by blue circles represent proteins overrepresented in the control group. Names of proteins functionally related to the complement system or S100A/ANXA protein families are included in D. Thresholds for significant adjusted P values were set according to the number of samples included in each comparison.