{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:01:03Z","timestamp":1790773263392,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1195451"],"award-info":[{"award-number":["1195451"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009845","name":"Ovarian Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009845","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004853","name":"Chinese University of Hong Kong","doi-asserted-by":"publisher","award":["IDBF23MED14"],"award-info":[{"award-number":["IDBF23MED14"]}],"id":[{"id":"10.13039\/501100004853","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ovarian cancer remains the most lethal gynaecological malignancy, largely due to late\u2010stage diagnosis and the limited sensitivity of CA\u2010125 for borderline and low\u2010grade tumours. Dysregulated lipid metabolism may provide complementary diagnostic information. This study aimed to develop lipid\u2010based biomarkers to improve the differential diagnosis of adnexal masses. We profiled total plasma and small extracellular vesicle (sEV) lipids in women with benign, borderline and malignant ovarian tumours, using healthy women as controls. Solid\u2010phase extraction demonstrated superior reproducibility, lipid\u2010class specificity and sEV lipid enrichment compared with liquid\u2010liquid extraction. Combined with CA\u2010125, both plasma and sEV lipid biomarkers outperformed CA\u2010125 alone for distinguishing borderline and low\u2010grade serous ovarian cancer from benign tumours (accuracy up to 0.89\u00a0vs. 0.67). In patients with normal CA\u2010125 levels, sEV lipids provided the greatest diagnostic advantage, distinguishing invasive and borderline tumours from benign adnexal masses (AUROC up to 0.82). Generative artificial intelligence was used to simulate biomarker performance in synthetic cohorts for differential diagnosis (\n                    <jats:italic>n<\/jats:italic>\n                    = 10,000) and screening (\n                    <jats:italic>n<\/jats:italic>\n                    = 100,000). For differential diagnosis, sEV lipids combined with CA\u2010125 outperformed plasma lipids for identifying endometrioid and mucinous ovarian cancer from benign adnexal masses. For screening, sEV lipids alone achieved accuracies of 0.91 and 0.94 for benign conditions and high\u2010grade serous ovarian cancer, respectively. Simulations restricted to patients with normal CA\u2010125 levels confirmed that sEV lipids provided the highest discriminative performance for low\u2010grade serous ovarian cancer (AUROC up to 0.74), demonstrating their potential where CA\u2010125 alone fails. To the best of our knowledge, this is the first study to directly compare matched plasma and sEV lipid profiles across ovarian cancer histotypes, demonstrating a diagnostic advantage for sEV lipids\u2014particularly for borderline, low\u2010grade serous and mucinous tumours, supporting their integration alongside CA\u2010125 in future differential diagnosis and screening strategies.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70348","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:06:03Z","timestamp":1788314763000},"source":"Crossref","is-referenced-by-count":0,"title":["Small Extracellular Vesicle and Total Lipid Profiles Provide a Diagnostic Advantage Over CA\u2010125 Across Ovarian Cancer Subtypes"],"prefix":"10.1002","volume":"15","author":[{"given":"Shikha","family":"Rani","sequence":"first","affiliation":[{"name":"Translational Extracellular Vesicles in Obstetrics and Gynae\u2010Oncology Group Frazer Institute Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"},{"name":"UQ Centre for Extracellular Vesicle Nanomedicine Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7913-5749","authenticated-orcid":false,"given":"Dominic","family":"Guanzon","sequence":"additional","affiliation":[{"name":"Translational Extracellular Vesicles in Obstetrics and Gynae\u2010Oncology Group Frazer Institute Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"},{"name":"UQ Centre for Extracellular Vesicle Nanomedicine Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Lai","sequence":"additional","affiliation":[{"name":"Translational Extracellular Vesicles in Obstetrics and Gynae\u2010Oncology Group Frazer Institute Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"},{"name":"UQ Centre for Extracellular Vesicle Nanomedicine Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherin","family":"Scholz\u2010Romero","sequence":"additional","affiliation":[{"name":"Translational Extracellular Vesicles in Obstetrics and Gynae\u2010Oncology Group Frazer Institute Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"},{"name":"UQ Centre for Extracellular Vesicle Nanomedicine Faculty of Health, Medicine and Behavioural Sciences The University of Queensland  Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"Perrin","sequence":"additional","affiliation":[{"name":"Mater Research Institute Translational Research Institute The University of Queensland  Woolloongabba Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan","family":"Lourie","sequence":"additional","affiliation":[{"name":"Mater Research Institute Translational Research Institute The University of Queensland  Woolloongabba Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhavi","family":"Joshi","sequence":"additional","affiliation":[{"name":"Frazer institute Faculty of Medicine The University of Queensland Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"McCart Reed","sequence":"additional","affiliation":[{"name":"Frazer institute Faculty of Medicine The University of Queensland Herston Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaltin","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Mater Research Institute Translational Research Institute The University of Queensland  Woolloongabba Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aase","family":"Handberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Faculty of Medicine The Chinese University of Hong Kong  Sha Tin Hong Kong SAR China"},{"name":"JC STEM Lab Li Ka Shing Institute of Health Sciences Faculty of Medicine The Chinese University of Hong Kong  Sha Tin Hong Kong SAR 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