Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer

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Authors	VYHLÍDALOVÁ KOTRBOVÁ Anna GÖMÖRYOVÁ Kristína MIKULOVÁ Antónia PLEŠINGEROVÁ Hana SLADEČEK Stanislava KRAVEC Marek HRACHOVINOVÁ Šárka POTĚŠIL David DUNSMORE Garett BLERIOT Camille BIED Mathilde KOTOUČEK Jan BEDNAŘÍKOVÁ Markéta HAUSNEROVÁ Jitka MINÁŘ Luboš CRHA Igor FELSINGER Michal ZDRÁHAL Zbyněk GINHOUX Florent WEINBERGER Vít BRYJA Vítězslav HLAVÁČKOVÁ POSPÍCHALOVÁ Vendula
Year of publication	2024
Type	Article in Periodical
Magazine / Source	Journal of Extracellular Vesicles
MU Faculty or unit	Faculty of Science
Citation
Web	https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12420
Doi	http://dx.doi.org/10.1002/jev2.12420
Keywords	ascites; extracellular vesicles (EV); fallopian tube and peritoneum (HGSC); high-grade serous carcinoma of the ovary; macrophage; ovarian cancer (OC); tandem mass spectrometry (MS/MS); tumour microenvironment (TME)
Attached files	2392978.pdf
Description	High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.
Related projects:	Modernization of the Czech Infrastructure for Integrative Structural Biology Comprehensive genomic profiling in ovarian cancer patients treated with platinumbased chemotherapy: identification of predictive biomarkers and evaluation of the potential of precision oncology approach The potential of ascites in ovarian cancer research National institute for cancer research CIISB - Czech Infrastructure for Integrative Structural Biology