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Tumor Biology

, Volume 35, Issue 9, pp 8795–8799 | Cite as

Serum and bronchial aspiration fluid HE-4 levels in lung cancer

  • Elif Yilmazel Ucar
  • Alev Lazoglu Ozkaya
  • Omer Araz
  • Metin Akgun
  • Mehmet Meral
  • Hasan Kaynar
  • Leyla Saglam
  • Hulya Aksoy
  • Fatih Akcay
Research Article

Abstract

Human epididymis 4 (HE-4) protein has been proposed as a tumor marker for lung and ovarian cancer. This study was designed to measure HE-4 levels in bronchial aspiration fluid (BAF) of patients with lung cancer and to describe the relationship of BAF HE-4 with known systemic increase in serum HE-4 levels. Sixty-four patients with lung cancer, 38 with benign lung disease and 19 healthy subjects, were enrolled in our study. The BAF was obtained during routine bronchoscopic procedure in patient groups. HE-4 levels in serum and BAF were measured with the commercially available kit by an enzyme-linked immunosorbent assay. Serum HE-4 levels were significantly higher in patients with lung cancer group (204.2 ± 22.9 pmol/L) than in benign lung disease group (135 ± 26.9 pmol/L, p = 0.001) and healthy subjects (14.8 ± 7.0 pmol/L, p < 0.0001). No significant difference was observed in terms of BAF HE-4 values in two patient groups. BAF HE-4 levels were significantly higher than those of serum levels in both patient groups (p < 0.0001). Serum HE-4 level was correlated with tumor stage (p = 0.001) and age (p < 0.0001) in the lung cancer group. The areas under the receiver operating characteristic (ROC) curve of serum HE-4 was 0.784 (95 % confidence interval (CI), 0.701–0.867) and that of BAF HE-4 was 0.496 (95 % CI, 0.382–0.610). This study shows that a systemic increase in serum of HE-4 is more prominent than a local increase of HE-4 (BAF), so this may suggest the feasibility of using serum instead of BAF samples for HE-4 measurements in lung cancer cases.

Keywords

Lung cancer Human epididymis 4 Bronchial aspiration fluid Serum 

Notes

Acknowledgments

This study is supported by Scientific Research Projects at Ataturk University.

Conflicts of interest

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–128.CrossRefPubMedGoogle Scholar
  3. 3.
    Roth K, Hardie JA, Andreassen AH, Leh F, Eagan TM. Predictors of diagnostic yield in bronchoscopy: a retrospective cohort study comparing different combinations of sampling techniques. MBC Pulm Med. 2007;8:2.CrossRefGoogle Scholar
  4. 4.
    Baaklini WA, Reinoso MA, Gorin AB, Sharafkaneh A, Manian P. Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules. Chest. 2000;117:1049–54.CrossRefPubMedGoogle Scholar
  5. 5.
    Lee HS, Kwon SY, Kim KD, Yoon HI, Lee SM, Lee JH, et al. Determinants of diagnostic bronchial washing in peripheral lung cancer. Int J Tuberc Lung Dis. 2007;11:227–32.PubMedGoogle Scholar
  6. 6.
    Hirsch FR, Merrick DT, Franklin WA. Role of biomarker for early detection of lung cancer and chemoprevention. Eur Respir J. 2009;19:1151–8.CrossRefGoogle Scholar
  7. 7.
    Bouchard D, Morisset D, Bourbonnais Y, Tremblay GM. Proteins with whey-acidic-protein motifs and cancer. Lancet Oncol. 2006;7:167–74.CrossRefPubMedGoogle Scholar
  8. 8.
    Bingle L, Singleton V, Bingle CD. The putative ovarian tumour marker gene HE4(WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene. 2002;21:2768–73.CrossRefPubMedGoogle Scholar
  9. 9.
    Kirchhoff C, Habben I, Ivell R, Krull N. A major human epididymis specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod. 1991;45:350–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Hegmans JP, Veltman JD, Fung ET, Verch T, Glover C, Zhang F, et al. Protein profiling of pleural effusions to identify malignant pleural mesothelioma using SELDI-TOF MS. Technol Cancer Res Treat. 2009;8:323–32.CrossRefPubMedGoogle Scholar
  11. 11.
    Hertlein L, Stieber P, Kirschenhofer A, Krocker K, Nagel D, Lenhard M, et al. Human epididymis protein 4 (HE4) in benign and malignant diseases. Clin Chem Lab Med. 2012;50:2181–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Molina R, Escudero JM, Auge JM, Filella X, Foj L, Torne A, et al. HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumor Biol. 2011;32:1087–95.CrossRefGoogle Scholar
  13. 13.
    Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65:2162–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Hynninen J, Auranen A, Dean K, Lavonius M, Carpen O, Perheentupa A, et al. Serum HE4 profile during primary chemotherapy of epithelial ovarian cancer. Int J Gynecol Cancer. 2011;21:1573–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Hellström I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res. 2003;63:3695–700.PubMedGoogle Scholar
  16. 16.
    Tokuishi K, Yamashita SI, Ohbo K, Kawahara K. Splice variant HE4-V3 expression is associated with favorable prognosis in pulmonary adenocarcinoma. Tumor Biol. 2012;33:103–9.CrossRefGoogle Scholar
  17. 17.
    Detterbeck FC, Postmus PE, Tanoue LT. The stage classification of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e191S–210S.CrossRefPubMedGoogle Scholar
  18. 18.
    Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e142S–65S.CrossRefPubMedGoogle Scholar
  19. 19.
    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.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Galgano MT, Hampton GM, Frierson Jr HF. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Mod Pathol. 2006;19:847–53.PubMedGoogle Scholar
  21. 21.
    Speeckaert MM, Speeckaert R, Delanghe JR. Human epididymis protein 4 in cancer diagnostics: a promising and reliable tumor marker. Adv Clin Chem. 2013;59:1–21.CrossRefPubMedGoogle Scholar
  22. 22.
    Escudero JM, Auge JM, Filella X, Torne A, Pahisa J, Molina R. Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases. Clin Chem. 2011;57:1534–44.CrossRefPubMedGoogle Scholar
  23. 23.
    Yamashita S, Tokuishi K, Moroga T, Yamamoto S, Ohbo K, Miyahara S, et al. Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression. Tumor Biol. 2012;33:2365–70.CrossRefGoogle Scholar
  24. 24.
    Yamashita S, Tokuishi K, Hashimoto T, Moroga T, Kamei M, Ono K, et al. Prognostic significance of HE4 expression in pulmonary adenocarcinoma. Tumor Biol. 2011;32:265–71.CrossRefGoogle Scholar
  25. 25.
    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. Tumor Biol. 2012;33:1141–9.CrossRefGoogle Scholar
  26. 26.
    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. 2013;17:1346–53.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Elif Yilmazel Ucar
    • 1
  • Alev Lazoglu Ozkaya
    • 2
  • Omer Araz
    • 1
  • Metin Akgun
    • 1
  • Mehmet Meral
    • 1
  • Hasan Kaynar
    • 1
  • Leyla Saglam
    • 1
  • Hulya Aksoy
    • 2
  • Fatih Akcay
    • 2
  1. 1.Department of Pulmonary Diseases, School of MedicineAtaturk UniversityErzurumTurkey
  2. 2.Department of Biochemistry, School of MedicineAtaturk UniversityErzurumTurkey

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