{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:07:29Z","timestamp":1784268449591,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objective: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity; however, reliable first-trimester biomarkers are limited. Growth arrest-specific protein 6 (Gas6), a vitamin K-dependent ligand for the TAM receptor family (Tyro3, AXL, and MerTK), is crucial for trophoblast invasion and placental remodeling. This study evaluated whether first-trimester serum Gas6 levels differed between women with PE and controls and assessed the predictive utility across phenotypes. Methods: Participants were enrolled prospectively during routine first-trimester screening at 11 + 0 to 13 + 6 weeks, and cases and controls were selected using a nested case\u2013control design after pregnancy outcomes were known. ROC-derived cut-off values for Gas6 were selected retrospectively using the Youden index and were considered exploratory. The PE group was divided into early (n = 15, &lt;34 weeks) and late onset (n = 65, \u226534 weeks) subgroups. ELISA measured serum Gas6. Mann\u2013Whitney U, Kruskal\u2013Wallis, Spearman\u2019s correlation, ROC analysis, and multivariate logistic regression were applied. Results: Gas6 levels were significantly lower in PE than controls (15.73 vs. 38.08 ng\/mL, p &lt; 0.001); control reference median (38.08 ng\/mL, IQR 27.62 to 49.14), decreasing progressively to late (20.07 ng\/mL) and early onset PE (6.45 ng\/mL; all p &lt; 0.001). ROC analysis showed the highest exploratory discrimination for early onset preeclampsia (AUC = 0.959, 95% CI: 0.923\u20130.995; sensitivity 93.3%, specificity 84.1% at a retrospectively selected cut-off of \u226413.82 ng\/mL), with more modest discrimination for overall PE (AUC = 0.762) and late onset PE (AUC = 0.708). Lower first-trimester Gas6 levels remained significantly associated with early onset PE after adjustment for maternal age and BMI (OR = 0.555, 95% CI: 0.412\u20130.748, p &lt; 0.001). Conclusions: Serum Gas6 levels in the first trimester are lower in PE, particularly in cases of early onset disease, highlighting its potential as a candidate biomarker that requires further prospective and external validation before any screening application can be considered.<\/jats:p>","DOI":"10.3390\/jcm15145604","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:32:17Z","timestamp":1784266337000},"page":"5604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["First-Trimester Maternal Serum Growth Arrest-Specific Protein 6 (Gas6) Levels for the Prediction of Preeclampsia"],"prefix":"10.3390","volume":"15","author":[{"given":"Zehra","family":"Y\u0131lmaz","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Private Practice, 55200 Samsun, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4725-043X","authenticated-orcid":false,"given":"Nazan","family":"Yurtcu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilay","family":"Karademir","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Sivas Cumhuriyet University, 58140 Sivas, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9889-5249","authenticated-orcid":false,"given":"Canan Soyer","family":"Cal\u0131skan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Samsun University Faculty of Medicine, Samsun Training and Research Hospital, 55090 Samsun, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samettin","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Samsun University Faculty of Medicine, Samsun Training and Research Hospital, 55090 Samsun, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/HYPERTENSIONAHA.117.10803","article-title":"Hypertensive Disorders of Pregnancy","volume":"72","author":"Brown","year":"2018","journal-title":"Hypertension"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-023-00425-6","article-title":"Pre-eclampsia","volume":"9","author":"Dimitriadis","year":"2023","journal-title":"Nat. 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