Skip to main content

Advertisement

Log in

Evaluating the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

We evaluated the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer (SCLC). Serum HE4 level was measured in serum samples from 30 healthy controls and 49 patients with SCLC using enzyme-linked immunosorbent assay. HE4 expression in tumor tissues was analyzed by immunohistochemical staining. The results show that serum HE4 level is significantly higher in SCLC patients than those in healthy controls, which is also the case in tumor tissues where strong intracytoplasmic staining is demonstrable. Using the optimal cutoff value of 84.19 pmol/l, serum HE4 level distinguishes SCLC patients from healthy controls with a sensitivity of 69.4 %, a specificity of 93.3 %, and the area under the receiver operating characteristic curve (AUC) of 0.85. Compared to other well-known tumor markers used in lung cancer diagnosis, HE4 shows the highest sensitivity (69.4 %, 34 of 49) and accuracy (78.5 %, 62 of 79) in diagnosing SCLC, and combinations with other tumor markers further increase the sensitivity and accuracy. These findings suggest that HE4 levels are greatly elevated in sera and tumor tissues of patients with SCLC and serum HE4 is a potential diagnostic marker for patients with SCLC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Jemal A, Thun MJ, Ries LA, Howe HL, Weir HK, Center MM, et al. Annual report to the nation on the status of cancer, 1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008;100(23):1672–94. doi:10.1093/jnci/djn389.

    Article  PubMed Central  PubMed  Google Scholar 

  2. van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378(9804):1741–55. doi:10.1016/S0140-6736(11)60165-7.

    Article  PubMed  Google Scholar 

  3. Chapman CJ, Thorpe AJ, Murray A, Parsy-Kowalska CB, Allen J, Stafford KM, et al. Immunobiomarkers in small cell lung cancer: potential early cancer signals. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17(6):1474–80. doi:10.1158/1078-0432.CCR-10-1363.

    Article  CAS  Google Scholar 

  4. Brower V. Biomarker studies abound for early detection of lung cancer. J Natl Cancer Inst. 2009;101(1):11–3. doi:10.1093/jnci/djn483.

    Article  CAS  PubMed  Google Scholar 

  5. Liu W, Yang J, Chi PD, Zheng X, Dai SQ, Chen H, et al. Evaluating the clinical significance of serum HE4 levels in lung cancer and pulmonary tuberculosis. Int J Tuberc Lung Dis Off J Int Union Tuberc Lung Dis. 2013;17(10):1346–53. doi:10.5588/ijtld.13.0058.

    Article  CAS  Google Scholar 

  6. Hellstrom I, Hellstrom KE. fTwo novel biomarkers, mesothelin and HE4, for diagnosis of ovarian carcinoma. Expert Opin Med Diagn. 2011;5(3):227–40. doi:10.1517/17530059.2011.559459.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Chang X, Ye X, Dong L, Cheng H, Cheng Y, Zhu L, et al. Human epididymis protein 4 (HE4) as a serum tumor biomarker in patients with ovarian carcinoma. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc. 2011;21(5):852–8. doi:10.1097/IGC.0b013e31821a3726.

    Article  Google Scholar 

  8. Yamashita S, Tokuishi K, Hashimoto T, Moroga T, Kamei M, Ono K, et al. Prognostic significance of HE4 expression in pulmonary adenocarcinoma. Tumour Biol J Int Soc Oncodev Biol Med. 2011;32(2):265–71. doi:10.1007/s13277-010-0118-5.

    Article  CAS  Google Scholar 

  9. Iwahori K, Suzuki H, Kishi Y, Fujii Y, Uehara R, Okamoto N, et al. Serum HE4 as a diagnostic and prognostic marker for lung cancer. Tumour Biol J Int Soc Oncodev Biol Med. 2012;33(4):1141–9. doi:10.1007/s13277-012-0356-9.

    Article  CAS  Google Scholar 

  10. Micke P, Faldum A, Metz T, Beeh KM, Bittinger F, Hengstler JG, et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer—what limits limited disease? Lung Cancer. 2002;37(3):271–6.

    Article  PubMed  Google Scholar 

  11. Chhikara N, Saraswat M, Tomar AK, Dey S, Singh S, Yadav S. Human epididymis protein-4 (HE-4): a novel cross-class protease inhibitor. PLoS One. 2012;7(11):e47672. doi:10.1371/journal.pone.0047672.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, et al. WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respir Res. 2006;7:61. doi:10.1186/1465-9921-7-61.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Galgano MT, Hampton GM, Frierson Jr HF. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol Off J U S Can Acad Pathol Inc. 2006;19(6):847–53. doi:10.1038/modpathol.3800612.

    CAS  Google Scholar 

  14. Okamura K, Takayama K, Izumi M, Harada T, Furuyama K, Nakanishi Y. Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer. Lung Cancer. 2013;80(1):45–9. doi:10.1016/j.lungcan.2013.01.002.

    Article  PubMed  Google Scholar 

  15. Seemann MD, Beinert T, Furst H, Fink U. An evaluation of the tumour markers, carcinoembryonic antigen (CEA), cytokeratin marker (CYFRA 21-1) and neuron-specific enolase (NSE) in the differentiation of malignant from benign solitary pulmonary lesions. Lung Cancer. 1999;26(3):149–55.

    Article  CAS  PubMed  Google Scholar 

  16. Ghosh I, Bhattacharjee D, Das AK, Chakrabarti G, Dasgupta A, Dey SK. Diagnostic role of tumour markers CEA, CA15-3, CA19-9 and CA125 in lung cancer. Indian J Clin Biochem IJCB. 2013;28(1):24–9. doi:10.1007/s12291-012-0257-0.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the grant from Dean Fund of 302 Hospital of PLA (no. YNKT2012038).

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Huaming Wang or Wenchao Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, X., Fan, Y., Wang, J. et al. Evaluating the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer. Tumor Biol. 35, 6847–6853 (2014). https://doi.org/10.1007/s13277-014-1943-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1943-8

Keywords

Navigation