ArticleClinics (Sao Paulo, Brazil)2026
Serum human epididymis protein 4 and long-term mortality in U.S. women: a nationally representative cohort study.
Article in Clinics (Sao Paulo, Brazil), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeSerum Human Epididymal secretory protein E4 (HE4) is a biomarker in gynecologic oncology and is increasingly linked to fibrosis and adverse outcomes across organ systems; however, its population-level prognostic value beyond cancer and advanced organ failure remains unclear. PATIENTS AND
methodsWe analyzed women aged ≥ 20-years in the National Health and Nutrition Examination Survey (NHANES) 2001-2002 cycle with serum HE4 (unweighted n = 2200; weighted population ≈46.9 million) linked to mortality outcomes through 2019.
resultsOver a median 199.3-months of follow-up, 466 deaths occurred. Higher ln-HE4 levels were strongly associated with Chronic Kidney Disease (CKD) (Odds Ratio [OR = 2.07], 95% CI: 1.38-3.12) and history of lung disease (OR = 1.34, 95% CI: 1.06-1.71). In fully adjusted models, higher ln-HE4 was associated with all-cause mortality (Hazard Ratio [HR = 1.29], 95% CI: 1.03-1.63) and cancer mortality (HR = 1.60, 95% CI: 1.02-2.49). Chronic lower respiratory disease mortality showed a positive but imprecise association because of limited events (n = 25; HR = 3.16, 95% CI: 1.26-7.91). For diabetes mortality, the estimate was also imprecise and not statistically significant (n = 18; HR = 3.84, 95% CI: 0.92-16.00). Trends across quartiles were significant for all-cause (p for trend = 0.001) and cancer mortality (p for trend = 0.006). Sensitivity analyses were broadly consistent, although estimates for outcomes with few events should be interpreted cautiously.
conclusionsIn a nationally representative cohort of U.S. women, higher serum HE4 was associated with increased risks of all-cause and cancer mortality. Associations with chronic lower respiratory disease and diabetes mortality were based on few events and should be interpreted cautiously. These results support HE4 as a potential population-level prognostic biomarker beyond oncology, warranting validation in other cohorts and mechanistic studies.
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