Francesca Gorini, Camelia Alexandra Coada, Sarah Monesmith, Antonio De Leo, Dario de Biase, Giulia Dondi, Stella Di Costanzo, Francesco Mezzapesa, Ivan Vannini, Mattia Melloni, Sara Bandini, Flora Guerra, Riccardo Di Corato, Pierandrea De Iaco, Patrizia Hrelia, Anna Myriam Perrone, Sabrina Angelini, Gloria Ravegnini
{"title":"Distinctive features of blood- and ascitic fluid-derived extracellular vesicles in ovarian cancer patients.","authors":"Francesca Gorini, Camelia Alexandra Coada, Sarah Monesmith, Antonio De Leo, Dario de Biase, Giulia Dondi, Stella Di Costanzo, Francesco Mezzapesa, Ivan Vannini, Mattia Melloni, Sara Bandini, Flora Guerra, Riccardo Di Corato, Pierandrea De Iaco, Patrizia Hrelia, Anna Myriam Perrone, Sabrina Angelini, Gloria Ravegnini","doi":"10.1186/s10020-025-01177-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a highly aggressive malignancy characterized by early dissemination of cancer cells from the surface of the ovary to the peritoneum. To gain a deeper understanding of the mechanisms associated with this intraperitoneal spread, we aimed to characterize the role of extracellular vesicles (EVs) in metastatic colonization in OC.</p><p><strong>Methods: </strong>To this purpose, a total of 150 samples of ascitic fluids, blood serum, tumor and normal tissues from 60 OC patients, were extensively analyzed to characterize the EVs released in blood and ascitic fluids of OC patients, in terms of size, expression of superficial epitopes and abundance of miRNAs biocargo.</p><p><strong>Results: </strong>A statistically significant difference in the size of EVs derived from ascitic fluid and serum was identified. Analysis of surface protein expression highlighted twenty epitopes with a significant difference between the two biological matrices, of which 18 were over- and two were under-expressed in ascitic fluid. With regard to miRNA levels, Principal Component Analysis (PCA) assessed four distinct clusters representing tumor tissue, normal tissue, ascitic fluid, and serum. A prominent difference in circulating miRNAs was observed in serum and ascitic fluid highlighting 98 miRNAs significantly deregulated (P-adj < 0.05) between the two bodily fluids. Deregulated miRNAs and epitopes underline an enrichment in ascites in components contributing to the metastatic spread.</p><p><strong>Conclusion: </strong>The results highlight a clear difference between the two biological fluids, suggesting that tumor selectively releases specific EVs populations in serum or ascites. In this context, it seems that ascites-derived EVs play a major role in modulating EMT and metastatic cascade, which is a key feature of OC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"143"},"PeriodicalIF":6.0000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12010555/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-025-01177-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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Abstract
Background: Ovarian cancer (OC) is a highly aggressive malignancy characterized by early dissemination of cancer cells from the surface of the ovary to the peritoneum. To gain a deeper understanding of the mechanisms associated with this intraperitoneal spread, we aimed to characterize the role of extracellular vesicles (EVs) in metastatic colonization in OC.
Methods: To this purpose, a total of 150 samples of ascitic fluids, blood serum, tumor and normal tissues from 60 OC patients, were extensively analyzed to characterize the EVs released in blood and ascitic fluids of OC patients, in terms of size, expression of superficial epitopes and abundance of miRNAs biocargo.
Results: A statistically significant difference in the size of EVs derived from ascitic fluid and serum was identified. Analysis of surface protein expression highlighted twenty epitopes with a significant difference between the two biological matrices, of which 18 were over- and two were under-expressed in ascitic fluid. With regard to miRNA levels, Principal Component Analysis (PCA) assessed four distinct clusters representing tumor tissue, normal tissue, ascitic fluid, and serum. A prominent difference in circulating miRNAs was observed in serum and ascitic fluid highlighting 98 miRNAs significantly deregulated (P-adj < 0.05) between the two bodily fluids. Deregulated miRNAs and epitopes underline an enrichment in ascites in components contributing to the metastatic spread.
Conclusion: The results highlight a clear difference between the two biological fluids, suggesting that tumor selectively releases specific EVs populations in serum or ascites. In this context, it seems that ascites-derived EVs play a major role in modulating EMT and metastatic cascade, which is a key feature of OC.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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