{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T20:36:53Z","timestamp":1757623013715,"version":"3.44.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Human epididymis protein 4 (HE4), a potential novel biomarker for cancers, has been widely used in clinical practice, but evidence of its prognostic value for non\u2013small cell lung cancer (NSCLC) remain insufficient. This study aimed to explore the predictive value of serum HE4 levels on detecting recurrence or metastasis and cancer death among patients with NSCLC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We included 102 cases of confirmed NSCLC and 99 healthy control individuals in our cohort study. Venous blood samples from these fasting participants were extracted upon admission for testing serum HE4 levels. Cox regression analysis was used to evaluate the risk of end point events (recurrence or metastasis and cancer death) during a 3-year follow-up.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among the patients with NSCLC, Kaplan-Meier analysis showed that individuals with median serum HE4 levels of 177.84 pmol\/L or higher had much higher risk of recurrence or metastasis and cancer death than did individuals with median serum HE4 levels below 177.84 pmol\/L (P\u2005&amp;lt;\u2005.005). An adjusted model by Cox regression analysis suggested strong associations between serum HE4 levels and recurrence or metastasis (hazard ratio, 2.9 [95% CI, 1.8-6.2], P\u2005&amp;lt;\u2005.01) and cancer death (hazard ratio, 3.8 [95% CI, 2.5-7.9], P\u2005&amp;lt;\u2005.01) after confounding variables, including age, sex, smoking history, drinking history and treatment methods, were adjusted for. Furthermore, receiver operating characteristic curve analysis showed that the diagnostic model combining 4 biomarkers\u2014HE4, carcinoembryonic antigen, cytokeratin 19 fragment antigen, and squamous cell carcinoma antigen\u2014exhibited the largest area under the curve (0.996) for diagnosing composite events, with 96.2 % sensitivity and 98.4% specificity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>There was an independent correlation between high serum HE4 levels at admission and an increased risk of recurrence or metastasis and cancer death from NSCLC that supports serum HE4 as a biomarker for survival prognosis after NSCLC treatment.<\/jats:p>\n               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