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We conducted a multi-level interrogation of lipid metabolic phenotypes in patients with adnexal masses, integrating quantitative lipidomics profiling of plasma and ascites with publicly-available tumor transcriptome data. Using Sciex Lipidyzer, we assessed concentrations of\u2009&gt;\u2009500 plasma lipids in two patient cohorts\u2014(i) a pilot set of 100 women with OC (50) or benign tumor (50), and (ii) an independent set of 118 women with malignant (60) or benign (58) adnexal mass. 249 lipid species and several lipid classes were significantly reduced in cases versus controls in both cohorts (FDR\u2009&lt;\u20090.05). 23 metabolites\u2014triacylglycerols, phosphatidylcholines, cholesterol esters\u2014were validated at Bonferroni significance (P\u2009&lt;\u20099.16\u2009\u00d7\u200910<jats:sup>\u20135<\/jats:sup>). Certain lipids exhibited greater alterations in early- (diacylglycerols) or late-stage (lysophospholipids) cases, and multiple lipids in plasma and ascites were positively correlated. Lipoprotein receptor gene expression differed markedly in OC versus benign tumors. Importantly, several plasma lipid species, such as DAG(16:1\/18:1), improved the accuracy of CA125 in differentiating early-stage OC cases from benign controls, and conferred a 15\u201320% increase in specificity at 90% sensitivity in multivariate models adjusted for age and BMI. This study provides novel insight into systemic and local lipid metabolic differences between OC and benign disease, further implicating altered lipid uptake in OC biology, and advancing plasma lipid metabolites as a complementary class of circulating biomarkers for OC diagnosis and triage.<\/jats:p>","DOI":"10.1038\/s41598-021-97433-x","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T10:04:04Z","timestamp":1631527444000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Quantitative global lipidomics analysis of patients with ovarian cancer versus benign adnexal mass"],"prefix":"10.1038","volume":"11","author":[{"given":"Matthew F.","family":"Buas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles W.","family":"Drescher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Urban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher I.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Bettcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitai C.","family":"Hait","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten B.","family":"Moysich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunle","family":"Odunsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Raftery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"97433_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","volume":"70","author":"RL Siegel","year":"2020","unstructured":"Siegel, R. 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