Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer

Béla Nagy, Harjit Pal Bhattoa, Zoltán Steiber, Mária Csobán, Mária Szilasi, Gábor Méhes, Mónika Müller, József Lázár, János Kappelmayer, Péter Antal-Szalmás

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Background: Human epididymis protein 4 (HE4) is a reliable tumor marker for ovarian cancer, but only limited data are available on HE4 levels in lung malignancies.

Methods: HE4 levels were measured at diagnosis in 98 men with lung cancer at different stages of the disease, and these results were compared to an age-matched healthy male cohort (n=98). The concentrations of classical tumor markers were also determined, and their efficacy was compared to that of HE4.

Results: Compared to healthy controls, patients with lung neoplasm showed significantly higher HE4 levels [118.2 (80.6-150.1) pmol/L vs. 62.2 (47.2-76.1) pmol/L; p<0.001]. Although age and smoking modulated HE4 levels in the healthy cohort, no such effect was observed in the patient population. The area under the receiver operating characteristic curve (ROC-AUC) for HE4 was 0.848 (95% CI 0.792-0.904) for differentiating lung cancer patients from healthy controls, with a cut-off value of 97.6 pmol/L (sensitivity: 64.3%, specificity: 95.9%). HE4 levels were significantly elevated in all stages of lung cancer, and even in patients without clinical symptoms (p<0.05), but no difference was found between the different histological subgroups. A significant correlation was found between HE4 values and the tumor size determined by CT/MRI (Spearman's ρ=0.227, p=0.030). The combination of HE4 with CEA and CA 125 considerably enhanced the diagnostic efficacy [ROC-AUC: 0.963 (95% CI 0.937-0.990), sensitivity: 91.8%, specificity: 92.8%].

Conclusions: Our data suggest that serum HE4, especially in combination with CEA and CA 125, qualifies as a surrogate diagnostic marker in men with lung cancer.

Original languageEnglish
Pages (from-to)1639-1648
Number of pages10
JournalClinical Chemistry and Laboratory Medicine
Issue number11
Publication statusPublished - Nov 19 2014



  • HE4
  • lung cancer
  • non-small cell lung cancer (NSCLC)
  • small cell lung cancer (SCLC)
  • tumor marker

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

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