{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:22:53Z","timestamp":1778617373448,"version":"3.51.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":49,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["450518177"],"award-info":[{"award-number":["450518177"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"White Foundation"},{"DOI":"10.13039\/100006800","name":"Honorable Tina Brozman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006800","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P50CA240243"],"award-info":[{"award-number":["P50CA240243"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015616","name":"Gray Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015616","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Team Detect Me If You Can"},{"name":"NCI","award":["b.\t1R03CA283252-01"],"award-info":[{"award-number":["b.\t1R03CA283252-01"]}]},{"name":"Mighty Moose 5K"},{"DOI":"10.13039\/100011495","name":"Massachusetts Life Sciences Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011495","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deborah and Robert First Family Fund"},{"DOI":"10.13039\/100003135","name":"Minnesota Ovarian Cancer Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003135","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Lilli and Seth Harris Endowed Chair for Ovarian Cancer"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hereditary breast and ovarian cancer syndrome (HBOC) is principally caused by germline mutations in\n                    <jats:italic>BRCA1<\/jats:italic>\n                    and\n                    <jats:italic>BRCA2<\/jats:italic>\n                    . However, most women with HBOC are undiagnosed, and some patients meeting clinical criteria for HBOC will have no identifiable mutation after genetic testing. Here, we deploy a lasso-based model to combine serum miRNA profiles with clinical data to identify women at elevated risk for ovarian cancer among a population of 1831 individuals enrolled in an institutional biobank. The miRNA and metadata variables are mapped to two-dimensional space using lasso, after which a linear classification model is trained to estimate \u201c\n                    <jats:italic>BRCA<\/jats:italic>\n                    ness\u201d and long-term risk of cancer. After tenfold cross-validation, the method offers a\n                    <jats:italic>BRCA<\/jats:italic>\n                    prediction AUC score of 0.98 (95% CI 0.94\u20131.0) and generalizes across subgroups stratified by age, cancer history, and racial\/ethnic group. To demonstrate the clinical relevance of this phenotype, we use the lasso-based model to assess 5-year ovarian cancer risk among an independent cohort of 1044 subjects agnostic to genetic testing results enrolled in a randomized clinical trial. In this unselected population, the output of the lasso-based model strongly correlates to the log 5-year relative risk of ovarian cancer (R\u2009=\u20090.93, 95% CI 0.83\u20130.97,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). When the model was used to predict future onset of ovarian cancer directly, the AUC offered was AUC\u2009=\u20090.75 (95% CI 0.70\u20130.78). Together, these data suggest the proposed model is a predictor of future ovarian cancer risk.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-45020-3","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:35:41Z","timestamp":1774334141000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A lasso-based model combining miRNA and clinical variables predicts future risk of breast and ovarian cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"James W.","family":"Webber","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Wollborn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudhanshu","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Alimena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryanna","family":"Testino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Stawiski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Fendler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipanjan","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin M.","family":"Elias","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"45020_CR1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ygyno.2009.02.017","volume":"113","author":"ACOG Committee on Practice Bulletins","year":"2009","unstructured":"ACOG Committee on Practice Bulletins. Hereditary breast and ovarian cancer syndrome. Gynecol. Oncol. 113, 6\u201311. https:\/\/doi.org\/10.1016\/j.ygyno.2009.02.017 (2009).","journal-title":"Gynecol. Oncol."},{"key":"45020_CR2","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1002\/cncr.29041","volume":"121","author":"J Mersch","year":"2015","unstructured":"Mersch, J. et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer 121, 269\u2013275. https:\/\/doi.org\/10.1002\/cncr.29041 (2015).","journal-title":"Cancer"},{"key":"45020_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1097\/PAP.0000000000000177","volume":"25","author":"LN Hoang","year":"2018","unstructured":"Hoang, L. N. & Gilks, B. C. Hereditary breast and ovarian cancer syndrome: Moving beyond BRCA1 and BRCA2. Adv. Anat. Pathol. 25, 85\u201395. https:\/\/doi.org\/10.1097\/PAP.0000000000000177 (2018).","journal-title":"Adv. Anat. 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JAMA 322, 652\u2013665. https:\/\/doi.org\/10.1001\/jama.2019.10987 (2019).","journal-title":"JAMA"},{"key":"45020_CR6","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1245\/s10434-012-2257-y","volume":"19","author":"B Drohan","year":"2012","unstructured":"Drohan, B., Roche, C. A., Cusack, J. C. Jr. & Hughes, K. S. Hereditary breast and ovarian cancer and other hereditary syndromes: Using technology to identify carriers. Ann. Surg. Oncol. 19, 1732\u20131737. https:\/\/doi.org\/10.1245\/s10434-012-2257-y (2012).","journal-title":"Ann. Surg. Oncol."},{"key":"45020_CR7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.breast.2022.06.003","volume":"65","author":"R Graffeo","year":"2022","unstructured":"Graffeo, R. et al. Moderate penetrance genes complicate genetic testing for breast cancer diagnosis: ATM, CHEK2, BARD1 and RAD51D. Breast 65, 32\u201340. https:\/\/doi.org\/10.1016\/j.breast.2022.06.003 (2022).","journal-title":"Breast"},{"key":"45020_CR8","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1002\/cam4.4541","volume":"11","author":"S Tatineni","year":"2022","unstructured":"Tatineni, S. et al. Racial and ethnic variation in multigene panel testing in a cohort of BRCA1\/2-negative individuals who had genetic testing in a large urban comprehensive cancer center. Cancer Med. 11, 1465\u20131473. https:\/\/doi.org\/10.1002\/cam4.4541 (2022).","journal-title":"Cancer Med."},{"key":"45020_CR9","doi-asserted-by":"publisher","first-page":"3350","DOI":"10.1038\/s41467-023-38925-4","volume":"14","author":"K Elias","year":"2023","unstructured":"Elias, K. et al. Identification of BRCA1\/2 mutation female carriers using circulating microRNA profiles. Nat. Commun. 14, 3350. https:\/\/doi.org\/10.1038\/s41467-023-38925-4 (2023).","journal-title":"Nat. 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Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic. Ann. Oncol. 27, 1532\u20131538. https:\/\/doi.org\/10.1093\/annonc\/mdw209 (2016).","journal-title":"Ann. Oncol."},{"key":"45020_CR13","doi-asserted-by":"publisher","first-page":"543","DOI":"10.2147\/CLEP.S206949","volume":"11","author":"N Armstrong","year":"2019","unstructured":"Armstrong, N., Ryder, S., Forbes, C., Ross, J. & Quek, R. G. A systematic review of the international prevalence of BRCA mutation in breast cancer. Clin. Epidemiol. 11, 543\u2013561. https:\/\/doi.org\/10.2147\/CLEP.S206949 (2019).","journal-title":"Clin. Epidemiol."},{"key":"45020_CR14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1158\/1940-6207.CAPR-23-0156","volume":"17","author":"S Alimena","year":"2024","unstructured":"Alimena, S. et al. Differences in serum miRNA profiles by race, ethnicity, and socioeconomic status: Implications for developing an equitable ovarian cancer screening test. Cancer Prev. Res. (Phila) 17, 177\u2013185. https:\/\/doi.org\/10.1158\/1940-6207.CAPR-23-0156 (2024).","journal-title":"Cancer Prev. Res. (Phila)"},{"key":"45020_CR15","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-23-1355","author":"L Wollborn","year":"2024","unstructured":"Wollborn, L. et al. Effects of clinical covariates on serum miRNA expression among women without ovarian cancer. Cancer Epidemiol. Biomark. Prev. https:\/\/doi.org\/10.1158\/1055-9965.EPI-23-1355 (2024).","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"45020_CR16","doi-asserted-by":"publisher","first-page":"147","DOI":"10.4137\/CIN.S17292","volume":"14","author":"E Mazzola","year":"2015","unstructured":"Mazzola, E., Blackford, A., Parmigiani, G. & Biswas, S. Recent enhancements to the genetic risk prediction model BRCAPRO. 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PLoS ONE 4, e7314. https:\/\/doi.org\/10.1371\/journal.pone.0007314 (2009).","journal-title":"PLoS ONE"},{"key":"45020_CR28","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.breast.2021.04.011","volume":"58","author":"F Ficarazzi","year":"2021","unstructured":"Ficarazzi, F., Vecchi, M., Ferrari, M. & Pierotti, M. A. Towards population-based genetic screenings for breast and ovarian cancer: A comprehensive review from economic evaluations to patient perspectives. Breast 58, 121\u2013129. https:\/\/doi.org\/10.1016\/j.breast.2021.04.011 (2021).","journal-title":"Breast"},{"key":"45020_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/jpm12081323","author":"NT Boutin","year":"2022","unstructured":"Boutin, N. T. et al. The evolution of a large biobank at Mass General Brigham. J. Pers. Med. https:\/\/doi.org\/10.3390\/jpm12081323 (2022).","journal-title":"J. Pers. 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Nucleic Acids Res. 51, W319\u2013W325. https:\/\/doi.org\/10.1093\/nar\/gkad392 (2023).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45020-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45020-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45020-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T20:03:47Z","timestamp":1778616227000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-45020-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["45020"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-45020-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"assertion":[{"value":"18 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"KME reports consulting for AOA Dx, Inc. KME, JWW, WF, and DC report research funding from Aspira Women\u2019s Health. KME, WF, and DC disclose being co-inventors of US patent 11214839B2 which addresses miRNAs for ovarian cancer diagnosis. The remaining authors report no relevant financial disclosures.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14813"}}