Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June-2023 Volume 25 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2023 Volume 25 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Detection of serum HE4 levels contributes to the diagnosis of lung cancer

  • Authors:
    • Jun Li
    • Yuzhu Li
    • Lijing Huo
    • Ruyi Sun
    • Xiao Liu
    • Quan Gu
    • Anping Li
    • Sugui Han
    • Hongmei Liu
    • Yufeng Li
    • Yumin Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Department of Radiology, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, Department of Clinical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China, Department of Neurology, Zunhua Renmin Hospital, Zunhua, Hebei 064200, P.R. China, Department of Medical Laboratory, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, Department of Medical Laboratory, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, Nuclear Medicine Clinical Laboratory, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, Nuclear Medicine Clinical Laboratory, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China, The Cancer Institute, Tangshan People's Hospital, Tangshan, Hebei 063000, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 255
    |
    Published online on: April 27, 2023
       https://doi.org/10.3892/ol.2023.13841
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Lung cancer (LC) is the most frequently diagnosed cancer and is the leading cause of cancer‑associated death. Serum markers that exhibit high sensitivity and specificity for LC may assist in the diagnosis and prognosis of LC. The banked serum samples from 599 individuals, including 201 healthy controls, 124 patients with benign lung diseases, and 274 LC cases, were used. The serum concentrations of biomarkers were determined by electrochemiluminescence immunoassay and chemiluminescence immunoassay. The results showed that the serum human epididymis secretory protein 4 (HE4) levels in the LC group were significantly higher than in the healthy and benign lung disease groups. The serum levels of HE4, NSE, and CYFRA21‑1 were significantly higher in patients with LC compared to those in the benign lung disease group. The area under the area under the curve (AUC) of HE4 for discriminating LC from healthy controls was 0.851 (95% CI, 0.818‑0.884) and 0.739 (95% CI, 0.695‑0.783), 0.747 (95% CI, 0.704‑0.790), 0.626 (95% CI, 0.577‑0.676), and 0.700 (95% CI, 0.653‑0.747) for NSE, CYFRA21‑1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 combined with NSE, CYFRA21‑1, SCC, and proGRP for cancer diagnosis was 0.896 (95% CI, 0.868‑0.923). In early LC, the AUC value of HE4 for discriminating early LC from healthy controls was 0.802 (95% CI, 0.758‑0.845), 0.728 (95% CI, 0.679‑0.778), 0.699 (95% CI, 0.646‑0.752), 0.605 (95% CI, 0.548‑0.662), and 0.685 (95% CI, 0.630‑0.739) for NSE, CYFRA21‑1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 with NSE, CYFRA21‑1, SCC, and proGRP for early LC was 0.867 (95% CI, 0.831‑0.903). Serum HE4 is a promising LC biomarker, particularly for early‑stage LC. Measuring serum HE4 levels may improve the diagnostic efficiency of LC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Imai H, Kaira K, Suzuki K, Anzai M, Tsuda T, Ishizuka T, Kuwako T, Naruse I, Nemoto K, Uchino J, et al: A phase II study of afatinib treatment for elderly patients with previously untreated advanced non-small-cell lung cancer harboring EGFR mutations. Lung Cancer. 126:41–47. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Brinkmeyer JK and Moore DC: Necitumumab for the treatment of squamous cell non-small cell lung cancer. J Oncol Pharm Pract. 24:37–41. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Horn L, Reck M and Spigel DR: The Future of immunotherapy in the treatment of small cell lung cancer. Oncologist. 21:910–921. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T and Dive C: Progress and prospects of early detection in lung cancer. Open Biol. 7:1700702017. View Article : Google Scholar : PubMed/NCBI

6 

Dickson JL, Horst C, Nair A, Tisi S, Prendecki R and Janes SM: Hesitancy around low-dose CT screening for lung cancer. Ann Oncol. 33:34–41. 2022. View Article : Google Scholar : PubMed/NCBI

7 

Li M, Zhang Y, Jiang L, Li Y, Li G, Zhou J, Yang C, Li X, Qu W, Chen Y, et al: New insights into the diagnostic characteristics and clinical application of serum biomarkers for lung cancer, and human epididymis protein 4 as a new biomarker? Neoplasma. 69:729–740. 2022. View Article : Google Scholar : PubMed/NCBI

8 

Chen Z, Liu X, Shang X, Qi K and Zhang S: The diagnostic value of the combination of carcinoembryonic antigen, squamous cell carcinoma-related antigen, CYFRA 21-1, neuron-specific enolase, tissue polypeptide antigen, and progastrin-releasing peptide in small cell lung cancer discrimination. Int J Biol Markers. 36:36–44. 2021. View Article : Google Scholar : PubMed/NCBI

9 

Kirchhoff C, Habben I, Ivell R and Krull N: A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod. 45:350–357. 1991. View Article : Google Scholar : PubMed/NCBI

10 

Bingle L, Singleton V and 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. 21:2768–2773. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR and Hecht JL: Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 65:2162–2169. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Li Y, Wang ZC, Luo L, Mu CY, Xu J, Feng Q, Li SB, Gu B, Ma P and Lan T: The clinical value of the combined detection of sEGFR, CA125 and HE4 for epithelial ovarian cancer diagnosis. Eur Rev Med Pharmacol Sci. 24:604–610. 2020.PubMed/NCBI

13 

Wang H, Liu P, Xu H and Dai H: Early diagonosis of ovarian cancer: Serum HE4, CA125 and ROMA model. Am J Transl Res. 13:14141–14148. 2021.PubMed/NCBI

14 

Plotti F, Guzzo F, Schirò T, Terranova C, De Cicco Nardone C, Montera R, Luvero D, Scaletta G, Lopez S, Capriglione S, et al: Role of human epididymis protein 4 (HE4) in detecting recurrence in CA125 negative ovarian cancer patients. Int J Gynecol Cancer. ijgc-2019-000211. 2019.(Epub ahead of print). View Article : Google Scholar

15 

Espiau Romera A, Coronado Martín PJ, Chóliz Ezquerro M, Cuesta Guardiola T, Adiego Calvo I and Baquedano Mainar L: Value of preoperative HE4 as predictor of advanced disease in endometrioid endometrial cancer. Int J Gynaecol Obstet. 153:64–70. 2021. View Article : Google Scholar : PubMed/NCBI

16 

Zeng Q, Liu M, Zhou N, Liu L and Song X: Serum human epididymis protein 4 (HE4) may be a better tumor marker in early lung cancer. Clin Chim Acta. 455:102–106. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Lamy PJ, Plassot C and Pujol JL: Serum HE4: An independent prognostic factor in non-small cell lung cancer. PLoS One. 10:e01288362015. View Article : Google Scholar : PubMed/NCBI

18 

Yang B, Ren N, Guo B, Xin H and Yin Y: Measuring serum human epididymis secretory protein autoantibody as an early biomarker of lung cancer. Transl Cancer Res. 9:735–741. 2020. View Article : Google Scholar : PubMed/NCBI

19 

Siegel RL, Miller KD, Wagle NS and Jemal A: Cancer statistics, 2023. CA Cancer J Clin. 73:17–48. 2023. View Article : Google Scholar : PubMed/NCBI

20 

Iwahori K, Suzuki H, Kishi Y, Fujii Y, Uehara R, Okamoto N, Kobayashi M, Hirashima T, Kawase I and Naka T: Serum HE4 as a diagnostic and prognostic marker for lung cancer. Tumour Biol. 33:1141–1149. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Liu W, Yang J, Chi PD, Zheng X, Dai SQ, Chen H, Xu BL and Liu WL: Evaluating the clinical significance of serum HE4 levels in lung cancer and pulmonary tuberculosis. Int J Tuberc Lung Dis. 17:1346–1353. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Nagy B Jr, Bhattoa HP, Steiber Z, Csobán M, Szilasi M, Méhes G, Müller M, Lázár J, Kappelmayer J and Antal-Szalmás P: Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer. Clin Chem Lab Med. 52:1639–1648. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Liu L, Liu B, Zhu LL, Zhang W and Li Y: Clinical significance of CYFRA21-1, Scc-Ag and telomerase activity in serum and pleural effusion of patients with squamous-cell lung cancer. Bioanalysis. 4:2367–2374. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Du J, Li Y, Wang L, Zhou Y, Shen Y, Xu F and Chen Y: Selective application of neuroendocrine markers in the diagnosis and treatment of small cell lung cancer. Clin Chim Acta. 509:295–303. 2020. View Article : Google Scholar : PubMed/NCBI

25 

Ucar EY, Ozkaya AL, Araz O, Akgun M, Meral M, Kaynar H, Saglam L, Aksoy H and Akcay F: Serum and bronchial aspiration fluid HE-4 levels in lung cancer. Tumour Biol. 35:8795–8799. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Hertlein L, Stieber P, Kirschenhofer A, Krocker K, Nagel D, Lenhard M and Burges A: Human epididymis protein 4 (HE4) in benign and malignant diseases. Clin Chem Lab Med. 50:2181–2188. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Gąsiorowska E, Magnowska M, Iżycka N, Warchoł W and Nowak-Markwitz E: The role of HE4 in differentiating benign and malignant endometrial pathology. Ginekol Pol. 87:260–264. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Jiang SW, Chen H, Dowdy S, Fu A, Attewell J, Kalogera E, Drapkin R, Podratz K, Broaddus R and Li J: HE4 transcription- and splice variants-specific expression in endometrial cancer and correlation with patient survival. Int J Mol Sci. 14:22655–22677. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Li J, Chen H, Mariani A, Chen D, Klatt E, Podratz K, Drapkin R, Broaddus R, Dowdy S and Jiang SW: HE4 (WFDC2) promotes tumor growth in endometrial cancer cell lines. Int J Mol Sci. 14:6026–6043. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li J, Li Y, Huo L, Sun R, Liu X, Gu Q, Li A, Han S, Liu H, Li Y, Li Y, et al: Detection of serum HE4 levels contributes to the diagnosis of lung cancer. Oncol Lett 25: 255, 2023.
APA
Li, J., Li, Y., Huo, L., Sun, R., Liu, X., Gu, Q. ... Zhang, Y. (2023). Detection of serum HE4 levels contributes to the diagnosis of lung cancer. Oncology Letters, 25, 255. https://doi.org/10.3892/ol.2023.13841
MLA
Li, J., Li, Y., Huo, L., Sun, R., Liu, X., Gu, Q., Li, A., Han, S., Liu, H., Li, Y., Zhang, Y."Detection of serum HE4 levels contributes to the diagnosis of lung cancer". Oncology Letters 25.6 (2023): 255.
Chicago
Li, J., Li, Y., Huo, L., Sun, R., Liu, X., Gu, Q., Li, A., Han, S., Liu, H., Li, Y., Zhang, Y."Detection of serum HE4 levels contributes to the diagnosis of lung cancer". Oncology Letters 25, no. 6 (2023): 255. https://doi.org/10.3892/ol.2023.13841
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Li Y, Huo L, Sun R, Liu X, Gu Q, Li A, Han S, Liu H, Li Y, Li Y, et al: Detection of serum HE4 levels contributes to the diagnosis of lung cancer. Oncol Lett 25: 255, 2023.
APA
Li, J., Li, Y., Huo, L., Sun, R., Liu, X., Gu, Q. ... Zhang, Y. (2023). Detection of serum HE4 levels contributes to the diagnosis of lung cancer. Oncology Letters, 25, 255. https://doi.org/10.3892/ol.2023.13841
MLA
Li, J., Li, Y., Huo, L., Sun, R., Liu, X., Gu, Q., Li, A., Han, S., Liu, H., Li, Y., Zhang, Y."Detection of serum HE4 levels contributes to the diagnosis of lung cancer". Oncology Letters 25.6 (2023): 255.
Chicago
Li, J., Li, Y., Huo, L., Sun, R., Liu, X., Gu, Q., Li, A., Han, S., Liu, H., Li, Y., Zhang, Y."Detection of serum HE4 levels contributes to the diagnosis of lung cancer". Oncology Letters 25, no. 6 (2023): 255. https://doi.org/10.3892/ol.2023.13841
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team