{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:56:54Z","timestamp":1775818614139,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Serum carcinoembryonic antigen (CEA) is a widely used biomarker in non-small cell lung cancer (NSCLC). However, its association with oncogenic driver alterations and prognostic significance across molecular subtypes in metastatic disease remains insufficiently defined. Materials and Methods: This retrospective multicenter study included 332 patients with metastatic NSCLC harboring oncogenic alterations (EGFR, ALK, ROS1, KRAS, and others) from eight oncology centers in T\u00fcrkiye. Baseline serum CEA levels measured at metastatic diagnosis were analyzed on the natural logarithmic scale. Associations between CEA levels, molecular subtypes, clinical features, and overall survival (OS) were evaluated using generalized linear models and Cox proportional hazards regression. Results: Baseline CEA levels differed significantly across molecular subtypes (p = 0.001), with EGFR-mutant tumors showing the highest median levels. Multivariable analysis identified driver alteration, histology, and metastatic burden as independent determinants of baseline CEA. Higher baseline CEA and metastatic site count were independently associated with increased mortality risk (HR 1.151 and 1.279 per unit increase, respectively; p &lt; 0.001), while female sex was protective (HR 0.626; p = 0.004). KRAS mutations were associated with poorer survival compared with EGFR (HR 2.370; p &lt; 0.001). Kaplan\u2013Meier analyses showed a consistent trend toward longer OS in patients with CEA &lt; 5 ng\/mL, with significance only in the rare alteration subgroup. Conclusions: Baseline CEA may reflect underlying tumor biology across molecular subtypes and are associated with survival outcomes in metastatic NSCLC. However, given the variability across subgroups and modest effect sizes, these findings should be interpreted with caution. Prospective studies evaluating longitudinal CEA dynamics are warranted.<\/jats:p>","DOI":"10.3390\/medicina62040718","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:08:12Z","timestamp":1775812092000},"page":"718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Carcinoembryonic Antigen Levels Across Molecular Subtypes and Their Clinical and Prognostic Implications in Metastatic Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-8517","authenticated-orcid":false,"given":"Ali","family":"Aytac","sequence":"first","affiliation":[{"name":"Medical Oncology Clinic, Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Sanliurfa 63320, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-9419","authenticated-orcid":false,"given":"Bilgin","family":"Demir","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ayd\u0131n Adnan Menderes University, Ayd\u0131n 09100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meltem Demirtas","family":"Gulmez","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ayd\u0131n Adnan Menderes University, Ayd\u0131n 09100, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-5567","authenticated-orcid":false,"given":"Hayati","family":"Arvas","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Dicle University, Diyarbak\u0131r 21000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuba Ugur","family":"Tuzcu","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara 06000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-2087","authenticated-orcid":false,"given":"Enes","family":"Erul","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara 06000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salih","family":"Tunbekici","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ege University, \u0130zmir 35000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2212-1412","authenticated-orcid":false,"given":"Tahir","family":"Yerlikaya","sequence":"additional","affiliation":[{"name":"Medical Oncology Clinic, Antalya State Hospital, Antalya 07000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4972-9367","authenticated-orcid":false,"given":"Sezai","family":"Tunc","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Harran University, \u015eanl\u0131urfa 63320, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-0942","authenticated-orcid":false,"given":"Halil Ibrahim","family":"Ellez","sequence":"additional","affiliation":[{"name":"Medical Oncology Clinic, Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Sanliurfa 63320, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2435-368X","authenticated-orcid":false,"given":"Yasemin Aydinalp","family":"Camadan","sequence":"additional","affiliation":[{"name":"Medical Oncology Clinic, Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Sanliurfa 63320, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-3926","authenticated-orcid":false,"given":"Kubra","family":"Canaslan","sequence":"additional","affiliation":[{"name":"Medical Oncology Clinic, Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Sanliurfa 63320, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3867-0793","authenticated-orcid":false,"given":"Rumeysa","family":"Colak","sequence":"additional","affiliation":[{"name":"Medical Oncology Clinic, Mehmet Akif Inan Training and Research Hospital, University of Health Sciences, Sanliurfa 63320, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuhat","family":"Urakci","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Dicle University, Diyarbak\u0131r 21000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-4444","authenticated-orcid":false,"given":"Elif Berna","family":"Koksoy","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara 06000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozan","family":"Yazici","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara 06000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-5046","authenticated-orcid":false,"given":"Ali","family":"Alkan","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0598-7284","authenticated-orcid":false,"given":"Ozgur","family":"Tanriverdi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Mu\u011fla S\u0131tk\u0131 Ko\u00e7man University, Mu\u011fla 48000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-713X","authenticated-orcid":false,"given":"Erdem","family":"Goker","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ege University, \u0130zmir 35000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-7999","authenticated-orcid":false,"given":"Ahmet","family":"Demirkazik","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ankara University, Ankara 06000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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Cancer"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/718\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:56:23Z","timestamp":1775814983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/62\/4\/718"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":19,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["medicina62040718"],"URL":"https:\/\/doi.org\/10.3390\/medicina62040718","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]}}}