{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:04:23Z","timestamp":1790856263373,"version":"4.1.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003009","name":"Science, Technology, & Innovation Funding Authority","doi-asserted-by":"crossref","award":["46282"],"award-info":[{"award-number":["46282"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Breast cancer remains a leading cause of cancer-related mortality worldwide, with obesity markedly increasing the risk in affected individuals. Liquid biopsy-based extracellular vesicles (EVs) offer a minimally invasive platform for molecular profiling of tumor-derived markers. Plasma small-EVs from obese, chemotherapy-na\u00efve breast cancer patients (n\u2009=\u200976; stages I\u2013III) and age-matched obese controls (n\u2009=\u200936) were enriched and characterized by high-resolution transmission electron microscopy, dynamic light scattering (DLS) and specific EV markers. Proteomic profile of the enriched small-EVs using nanoLC-MS\/MS identified Fibronectin 1 (FN1) and von Willebrand Factor (VWF) as candidate markers. Bioinformatics and STRING networks revealed interactions with Syndecan-2 (SDC2) and Galectin-3 (Gal-3). As an independent validation, western blot confirmed that FN1, VWF, and SDC2 were higher enriched in the small-EVs of breast cancer with different stages than in those of normal and that high content of small-EVs FN1 and SDC2 was primarily associated with the aggressive triple-negative breast cancer (TNBC) subtype. Interestingly, Gal-3 was reduced in small-EVs but elevated in breast carcinoma tissues and microvesicle (MV)-enriched EVs. Functionally, treatment with TNBC-derived plasma small-EVs not only downregulated expression of epithelial marker\n                    <jats:italic>CDH1, and<\/jats:italic>\n                    upregulated expression of the mesenchymal markers\n                    <jats:italic>ZEB2<\/jats:italic>\n                    and FN1 in low-invasive MCF-7 breast cancer cells, but also elevated expression of inflammatory and matrix-remodeling mediators (\n                    <jats:italic>Il-6<\/jats:italic>\n                    ,\n                    <jats:italic>Tnf-\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>Mmp-9<\/jats:italic>\n                    ) in BNL CL.2 normal liver cells. ROC-Plotter and drug\u2013gene interaction analyses indicated associations with therapy response, with approved compounds targeting FN1 and VWF. Overall, these findings reveal proteomic signatures of minimally invasive plasma small-EVs as promising markers associated with diagnosis, molecular subtyping, disease progression, and guiding therapeutic strategies in obese breast cancer patients.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0348500","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:26:50Z","timestamp":1778002010000},"page":"e0348500","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma small-extracellular vesicles\u2019 proteomic signature in neoadjuvant chemotherapy\u2013na\u00efve breast cancer patients"],"prefix":"10.1371","volume":"21","author":[{"given":"Amr Ahmed","family":"WalyEldeen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif Nasser","family":"Taha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah M.","family":"Gameel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liali Yousef","family":"Talat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebatallah","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6403-7345","authenticated-orcid":true,"given":"Sherif 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