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

Varování

Publikace nespadá pod Ústav výpočetní techniky, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.

Autoři	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
Rok publikování	2024
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of Extracellular Vesicles
Fakulta / Pracoviště MU	Přírodovědecká fakulta
Citace
www	https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12420
Doi	http://dx.doi.org/10.1002/jev2.12420
Klíčová slova	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)
Přiložené soubory	2392978.pdf
Popis	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.
Související projekty:	Modernizace České infrastruktury pro integrativní strukturní biologii Komplexní genomové profilování u pacientek s karcinomem ovaria léčených platinovými deriváty: identifikace prediktivních biomarkerů a ověření využitelnosti precizní onkologie The potential of ascites in ovarian cancer research Národní ústav pro výzkum rakoviny CIISB - Česká infrastruktura pro integrativní strukturní biologii