Advertisement

Tumor Biology

, Volume 35, Issue 5, pp 4901–4905 | Cite as

Detection of circulating antibodies to linear peptide antigens derived from ANXA1 and DDX53 in lung cancer

  • Weili Wang
  • Songlei Guan
  • Shilong Sun
  • Yonglong Jin
  • Kuang-Hui Lee
  • Yubing Chen
  • Jun Wei
Research Article

Abstract

The EarlyCDT®-Lung test was the first autoantibody-based diagnostic tool for lung cancer, which was developed with a panel of recombinant protein antigens. To confirm whether the antibody test developed with linear peptide antigens has a similar power to that developed with the whole protein molecules, the present work was then undertaken to develop an in-house enzyme-linked immunosorbent assay with linear peptide antigens derived from annexin A1 (ANXA1) and DEAD box protein 53 (DDX53), which have been used to develop the EarlyCDT®-Lung test. A total of 272 patients with non-small cell lung cancer (NSCLC) and 227 control subjects matched in age and smoking history were recruited. Student’s t test showed that the levels of circulating IgG to ANXA1-derived peptide antigens were significantly higher in patients with NSCLC than control subjects (t = 5.66, P < 0.0001), in which the increased anti-ANXA1 IgG levels were observed only in patients at stages I, II, or III, but not in those at stage IV. However, the levels of circulating IgG to DDX53-derived peptide antigens were not significantly altered in NSCLC (t = 1.78, P = 0.076). Receiver operating characteristic analysis showed that the sensitivity against specificity of >90 % was 23.7 % for ANXA1 IgG assay and 13.8 % for DDX53 IgG assay. This work suggests that the linear peptide antigen derived from ANXA1 may be suitable for the development of diagnostic tool for lung cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens.

Keywords

Autoantibody ANXA1 DDX53 Lung cancer Tumor immunity 

Notes

Acknowledgments

We thank the Third Affiliated Hospital of Harbin Medical University, Harbin 150040, China, for recruitment of patients with lung cancer. This work was supported by YingJi Biotechnology & Exploitation Ltd, Shenzhen, China, and by Glory Biomedical Co. Ltd, Taipei, Taiwan.

Conflicts of interest

None

References

  1. 1.
    Reuschenbach M, von Knebel DM, Wentzensen N. A systematic review of humoral immune responses against tumor antigens. Cancer Immunol Immunother. 2009;58:1535–44.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kobold S, Lütkens T, Cao Y, Bokemeyer C, Atanackovic D. Autoantibodies against tumor-related antigens: incidence and biologic significance. Hum Immunol. 2010;71:643–51.CrossRefPubMedGoogle Scholar
  3. 3.
    Liu W, Peng B, Lu Y, Xu W, Qian W, Zhang J-Y. Autoantibodies to tumor-associated antigens as biomarkers in cancer immunodiagnosis. Autoimmun Rev. 2011;10:331–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Järås K, Anderson K. Autoantibodies in cancer: prognostic biomarkers and immune activation. Expert Rev Proteomics. 2011;8:577–89.CrossRefPubMedGoogle Scholar
  5. 5.
    Piura E, Piura B. Autoantibodies to tumor-associated antigens in breast carcinoma. J Oncol. 2010;264926.Google Scholar
  6. 6.
    Piura E, Piura B. Autoantibodies to tailor-made panels of tumor-associated antigens in breast carcinoma. J Oncol. 2011;982425.Google Scholar
  7. 7.
    Zhong L, Coe SP, Stromberg AJ, Khattar NH, Jett JR, Hirschowitz EA. Profiling tumor-associated antibodies for early detection of non-small cell lung cancer. J Thorac Oncol. 2006;1:513–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Chapman C, Murray A, Chakrabarti J, Thorpe A, Woolston C, Sahin U, et al. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 2007;18:868–73.CrossRefPubMedGoogle Scholar
  9. 9.
    Tan HT, Low J, Lim SG, Chung MC. Serum autoantibodies as biomarkers for early cancer detection. FEBS J. 2009;276:6880–904.CrossRefPubMedGoogle Scholar
  10. 10.
    Lam S, Boyle P, Healey GF, Maddison P, Peek L, Murray A, et al. EarlyCDT-Lung: an immunobiomarker test as an aid to early detection of lung cancer. Cancer Prev Res (Phila). 2011;4:1126–34.CrossRefPubMedGoogle Scholar
  11. 11.
    Chapman CJ, Healey GF, Murray A, Boyle P, Robertson C, Peek LJ, et al. EarlyCDT®-Lung test: improved clinical utility through additional autoantibody assays. Tumour Biol. 2012;33:1319–26.CrossRefPubMedGoogle Scholar
  12. 12.
    Soussi T. TP53 mutations in human cancer: database reassessment and prospects for the next decade. Adv Cancer Res. 2011;110:107–39.CrossRefPubMedGoogle Scholar
  13. 13.
    Chen YT, Scanlan MJ, Sahin U, Türeci O, Gure AO, Tsang S, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA. 1997;94:1914–8.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Schubert U, Antón LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 2000;404:770–4.CrossRefPubMedGoogle Scholar
  15. 15.
    Ulanet DB, Torbenson M, Dang CV, Casciola-Rosen L, Rosen A. Unique conformation of cancer autoantigen B23 in hepatoma: a mechanism for specificity in the autoimmune response. Proc Natl Acad Sci USA. 2003;100:12361–6.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Liu L, Liu N, Liu B, Yang Y, Zhang Q, Zhang W, et al. Are circulating autoantibodies to ABCC3 transporter a potential biomarker for lung cancer? J Cancer Res Clin Oncol. 2012;138:1737–42.CrossRefPubMedGoogle Scholar
  17. 17.
    Ye L, Li X, Sun S, Guan S, Wang M, Guan X, et al. A study of circulating anti-CD25 antibodies in non-small cell lung cancer. Clin Transl Oncol. 2013;5:633–7.CrossRefGoogle Scholar
  18. 18.
    Zhang C, Ye L, Guan S, Jin S, Wang W, Sun S, et al. Autoantibodies against p16 protein-derived peptides may be a potential biomarker for non-small cell lung cancer. Tumour Biol. 2013. doi: 10.1007/s13277-013-1271-4.
  19. 19.
    Guan S, Liu B, Zhang C, Lee K-H, Sun S, Wei J. Circulating autoantibody to CD25 may be a potential biomarker for early diagnosis of esophageal squamous cell carcinoma. Clin Transl Oncol. 2013;15:825–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Ye L, Guan S, Zhang C, Lee K-H, Sun L, Wei J, et al. Circulating autoantibody to FOXP3 may be a potential biomarker for esophageal squamous cell carcinoma. Tumour Biol. 2013;34:1873–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Söllner J, Heinzel A, Summer G, Fechete R, Stipkovits L, Szathmary S, et al. Concept and application of a computational vaccinology workflow. Immunome Res. 2010;6 Suppl 2:S7.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wang P, Sidney J, Kim Y, Sette A, Lund O, Nielsen M, et al. Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics. 2010;11:568.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Mayerhofer K, Tempfer C, Kucera E, Hefler L, Zeisler H, Kainz C, et al. Humoral p53 antibody response is a prognostic parameter in ovarian cancer. Anticancer Res. 1999;19(1B):875–8.PubMedGoogle Scholar
  24. 24.
    Abendstein B, Daxenbichler G, Windbichler G, Zeimet AG, Geurts A, Sweep F, et al. Predictive value of uPA, PAI-1, HER-2 and VEGF in the serum of ovarian cancer patients. Anticancer Res. 2000;20(1B):569–72.PubMedGoogle Scholar
  25. 25.
    Goodell V, Salazar LG, Urban N, Drescher CW, Gray H, Swensen RE, et al. Antibody immunity to the p53 oncogenic protein is a prognostic indicator in ovarian cancer. J Clin Oncol. 2006;24:762–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Anderson KS, Wong J, Vitonis A, Crum CP, Sluss PM, Labaer J, et al. p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2010;19:859–68.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Radiobiology, School of Public HealthJilin UniversityChangchunChina
  2. 2.School of Life ScienceJilin Agriculture UniversityChangchunChina
  3. 3.Department of RadiotherapySecond Hospital of Jilin UniversityChangchunChina
  4. 4.Pei-Ling Guan-Si HospitalHsin-Fu Kuansi TownshipHsinchu CountyRomania
  5. 5.Department of Diabetes & Cardiovascular Science, University of the Highlands & IslandsCentre for Health ScienceInvernessUK

Personalised recommendations