{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:26:31Z","timestamp":1786854391684,"version":"build-2736575974"},"reference-count":26,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"crossref","award":["RS-2024-00512405"],"award-info":[{"award-number":["RS-2024-00512405"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2024-00512405"],"award-info":[{"award-number":["RS-2024-00512405"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"crossref","award":["RS-2023-00240924"],"award-info":[{"award-number":["RS-2023-00240924"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RS-2023-00240924"],"award-info":[{"award-number":["RS-2023-00240924"]}],"id":[{"id":"https:\/\/ror.org\/022c4zk48","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Ovarian cancer is the most lethal gynecologic malignancy, and CA-125 has limited early-stage sensitivity. We developed and evaluated Foretell Ovary, an ensemble machine-learning classifier that integrates tumor-educated-platelet RNA markers and routine hematologic parameters for non-invasive ovarian cancer detection, and compared it head-to-head with CA-125. Methods: A multi-site prospective cohort study enrolled 460 South Korean participants (67 ovarian cancer, 15 borderline ovarian tumors, 197 benign gynecological conditions, and 181 asymptomatic controls) at six clinical sites between September 2024 and March 2026. The cohort was split into training (n = 279) and independent test (n = 181) sets under a pre-specified ACTB cycle threshold \u2264 28 per-protocol rule (test n = 169). The classifier blended a random forest and two calibrated logistic-regression sub-models built on eight platelet RNA markers, 24 complete blood count parameters, and 30 marker-by-hematology combination features. Performance was assessed at a pre-frozen cutoff of 0.44 and compared against CA-125 (35 U\/mL cutoff) in a matched subset (n = 100). Results: Foretell Ovary achieved an area under the receiver operating characteristic curve (AUC) of 0.923, sensitivity of 87.5% (100.0% for Stage II\u2013IV), specificity of 89.0%, and negative predictive value of 97.7% in the test set. In the matched subset, Foretell Ovary outperformed CA-125 on every metric (AUC 0.839 vs. 0.723; sensitivity 85.0% vs. 65.0%), with the largest gap in pre-menopausal participants (+25 percentage points in sensitivity). A three-tier risk-grading scheme retained no ovarian cancer in the low-risk grade. Conclusions: Foretell Ovary offers more accurate non-invasive detection of ovarian cancer than CA-125, particularly in pre-menopausal women, offering the flexibility to be used alone or combined with CA-125. Prospective validation studies are warranted.<\/jats:p>","DOI":"10.3390\/cancers18162629","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"2629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Foretell Ovary: A Blood-Based Ensemble Algorithm Integrating Tumor-Educated Platelet RNA and Routine Hematology for Non-Invasive Ovarian Cancer Screening"],"prefix":"10.3390","volume":"18","author":[{"given":"Eunyong","family":"Ahn","sequence":"first","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9790-6735","authenticated-orcid":false,"given":"Se Ik","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9509-7578","authenticated-orcid":false,"given":"Sarah","family":"Kim","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjung","family":"Kim","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8023-6061","authenticated-orcid":false,"given":"Sungmin","family":"Park","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Ji","family":"Song","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6138-0130","authenticated-orcid":false,"given":"Hayoon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Ah","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Genomic Strategy, Samkwang Labtree, Seoul 06740, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-4021","authenticated-orcid":false,"given":"Yong Sang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Myongji Hospital, Goyang 10475, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-7065","authenticated-orcid":false,"given":"Jae-Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TaeJin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Foretell My Health, Inc., Pohang 37554, Republic of Korea"},{"name":"Department of Life Science, Handong Global University, Pohang 37554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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