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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 and Péter Antal-Szalmás EMAIL logo
Published/Copyright: May 15, 2014
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 52 Issue 11

Abstract

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.

Keywords: HE4; lung cancer; non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); tumor marker
Corresponding author: Péter Antal-Szalmás, MD, PhD, Department of Laboratory Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen 4032, Hungary, Phone: + 36 52 340006, Fax: + 36 52 417631, E-mail:
aBéla Nagy Jr and Harjit Pal Bhattoa contributed equally to this work.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: Béla Nagy Jr was supported by the János Bólyai Research Scholarship of the Hungarian Academy of Sciences. Harjit Pal Bhattoa was supported by the OTKA 105073 Research Grant. János Kappelmayer was supported by the TÁMOP 4.2.1./B-09/1/KONV-2010-0007 and the TÁMOP-4.2.2.A-11/1/KONV-2012-0025 projects. These latter projects are implemented through the New Hungary Development Plan, co-financed by the European Social Fund. Péter Antal-Szalmás was supported by the National Office for Research and Technology of Hungary (presently National Development Agency) (TECH-09-A1-2009-0113; mAB-CHIC).

Employment or leadership: Mónika Müller is an employee at the Adware Research Ltd., and József Lázár is employed by the Biosystem International Hungary Co.

Honorarium: None declared.

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Received: 2014-1-11
Accepted: 2014-4-9
Published Online: 2014-5-15
Published in Print: 2014-11-19

©2014 by De Gruyter

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https://doi.org/10.1515/cclm-2014-0041
Keywords for this article
HE4; lung cancer; non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); tumor marker

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. From symptoms to biomarkers: a change of paradigm
  4. Reviews
  5. Biochemical markers in early diagnosis and management of systemic amyloidoses
  6. The accuracy of the anti-mitochondrial antibody and the M2 subtype test for diagnosis of primary biliary cirrhosis: a meta-analysis
  7. Genetics and Molecular Diagnostics
  8. Selection of an optimal method for co-isolation of circulating DNA and miRNA from the plasma of pregnant women
  9. General Clinical Chemistry and Laboratory Medicine
  10. Harmonisation of seven common enzyme results through EQA
  11. Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience
  12. Adopting European Network for Health Technology Assessments (EunetHTA) core model for diagnostic technologies for improving the accuracy and appropriateness of blood gas analyzers’ assessment
  13. Impact of assay design on test performance: lessons learned from 25-hydroxyvitamin D
  14. Anti-ruthenium antibodies mimic macro-TSH in electrochemiluminescent immunoassay
  15. The relationship between the Spine Deformity Index, biochemical parameters of bone metabolism and vascular calcifications: results from the Epidemiological VERtebral FRACtures iTalian Study (EVERFRACT) in dialysis patients
  16. Quantification of polyclonal free light chains in clinical samples using a single turbidimetric immunoassay
  17. Global coagulation tests: their applicability for measuring direct factor Xa- and thrombin inhibition and reversal of anticoagulation by prothrombin complex concentrate
  18. Reference Values and Biological Variations
  19. The importance of individual biology in the clinical use of serum biomarkers for ovarian cancer
  20. The quality of diagnostic testing may be impaired during shipment of lithium-heparin gel tubes
  21. Cancer Diagnostics
  22. Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer
  23. Intestinal permeability in patients with metastatic colon cancer treated with patupilone
  24. Cardiovascular Diseases
  25. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay
  26. Infectious Diseases
  27. Early indicators of severity and construction of a risk model for prognosis based upon laboratory parameters in patients with hemorrhagic fever with renal syndrome
  28. Corrigendum
  29. Automated indirect immunofluorescence antinuclear antibody analysis is a standardized alternative for visual microscope interpretation
  30. Letters to the Editor
  31. The future of the laboratory information system – what are the requirements for a powerful system for a laboratory data management?
  32. Hypernatraemia in disguise
  33. Interference of therapeutic monoclonal immunoglobulins in the investigation of M-proteins
  34. The impact of exercise on the variation of serum free light chains
  35. Response to Jacobs: N Latex FLC serum free light-chain assays in patients with renal impairment
  36. Reply to Berlanga et al. (DOI 10.1515/cclm-2014-0420)
  37. Mean platelet volume in patients with non-alcoholic fatty liver disease: is mean platelet volume ready as a surrogate marker?
  38. False-positive D-dimer result in a latex-enhanced immunoassay caused by interfering human anti-mouse antibodies
  39. D-Dimer in normal pregnancy: determination of reference values for three commercially available assays
  40. Paraoxonase 2 sequence variation (c.311 C>G) is associated with a modest decrease in circulating LDL size in children and adolescents
  41. The effect of volume of hydrochloric acid preservation on 24-hour urinary catecholamine test
  42. Congress Abstracts
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  45. 46th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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