Tumor Biology

, Volume 33, Issue 4, pp 1141–1149 | Cite as

Serum HE4 as a diagnostic and prognostic marker for lung cancer

  • Kota Iwahori
  • Hidekazu Suzuki
  • Yoshiro Kishi
  • Yoshihiro Fujii
  • Rie Uehara
  • Norio Okamoto
  • Masashi Kobayashi
  • Tomonori Hirashima
  • Ichiro Kawase
  • Tetsuji Naka
Research Article


We evaluated the diagnostic and prognostic efficacy of human epididymis protein 4 (HE4) for lung cancer patients by using our novel enzyme-linked immunosorbent assay (ELISA) system. We measured serum HE4 levels of cancer patients including 49 lung cancer and 18 ovarian cancer patients. Furthermore, we evaluated the relationship between serum HE4 levels and overall survival after chemotherapy of 24 lung cancer patients. Serum HE4 levels were significantly higher for non-small, small cell lung cancer and ovarian cancer patients than for healthy controls. The area under the receiver operating characteristic curve (AUC) was calculated for differentiation of lung cancer patients and healthy controls. AUC for serum HE4 was 0.988 for differentiating lung cancer patients from healthy controls, with a cutoff value of 6.56 ng/ml (sensitivity = 89.8%, specificity = 100%). Serum HE4 levels were elevated in 36/40 (90.0%) non-small cell lung cancer patients, 8/9 (88.9%) small cell lung cancer patients and 8/18 (44.4%) ovarian cancer patients. High levels of serum HE4 (>15 ng/ml) after chemotherapy were significantly correlated with worse overall survival after the treatment. These findings suggest that serum HE4 is a potential diagnostic and prognostic marker for lung cancer patients.


HE4 Tumor marker ELISA Lung cancer Chemotherapy 



We appreciate Shintaro Nomura (Nagahama Institute of Bio-Science and Technology, Shiga, Japan) for providing helpful comments on immunohistochemical analysis, Barry Ripley for outstanding editing of the manuscript and Masako Ikeda for their technical assistance. We wish to thank Y. Ito, N. Kawakami and Y. Kanazawa for their secretarial assistance. This work was supported by a grant-in-aid from the Ministry of Health, Labour and Welfare, Japan.

Conflict of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Kota Iwahori
    • 1
    • 2
  • Hidekazu Suzuki
    • 3
  • Yoshiro Kishi
    • 4
  • Yoshihiro Fujii
    • 4
  • Rie Uehara
    • 4
  • Norio Okamoto
    • 3
  • Masashi Kobayashi
    • 3
  • Tomonori Hirashima
    • 3
  • Ichiro Kawase
    • 3
  • Tetsuji Naka
    • 1
  1. 1.Laboratory for Immune SignalNational Institute of Biomedical InnovationIbarakiJapan
  2. 2.Department of Respiratory Medicine, Allergy, and Rheumatic DiseasesOsaka University Graduate School of MedicineSuitaJapan
  3. 3.Department of Thoracic MalignancyOsaka Prefectural Medical Center for Respiratory and Allergic DiseasesHabikinoJapan
  4. 4.Medical & Biological Laboratories, Co., Ltd.NagoyaJapan

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