Skip to main content

Advertisement

Log in

Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non-small cell lung cancer

  • Original Article
  • Published:
Tumor Biology

Abstract

Biochemical markers play a significant role in the diagnosis of lung cancer. Recent studies have demonstrated a link involving S100 Calcium Binding Proteins (S100A2, S100A6) and non-small cell lung cancer (NSCLC), but the expediency of their serum levels in NSCLC has not been established. In this study, we evaluate the potential of serum S100A2 and S100A6 levels as diagnostic markers for NSCLC. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of S100A2 and S100A6 in 141 NSCLC patients and 150 healthy subjects. Serum levels of the two proteins in patients with NSCLC were higher compared to healthy controls (P = 0.0002 for S100A2 and P < 0.0001 for S100A6). Moreover, the levels of S100A2 and S100A6 were higher in the sera of stage I/II NSCLC patients compared to healthy controls with P = 0.01 and <0.0001, respectively. Receiver operating characteristic (ROC) analysis showed that S100A2 could distinguish NSCLC patients from healthy controls (AUC = 0.646), and S100A6 could also identify NSCLC (AUC = 0.668). Meanwhile, these two proteins showed notable capabilities for distinguishing stage I/II NSCLC from healthy controls (AUC = 0.708 for S100A2 and AUC = 0.702 for S100A6). Our results indicate that serum levels of S100A2 and S100A6 are significantly elevated in early stage NSCLC and may have the potential for NSCLC biomarker. Further studies with large sample population would help validate our findings.

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

Similar content being viewed by others

References

  1. Yu H, Han Z, Wang Y, Xin H. The clonal evolution and therapeutic approaches of lung cancer. Cell Biochem Biophys. 2014;70:63–71.

    Article  CAS  PubMed  Google Scholar 

  2. Travis WD. Classification of lung cancer. Semin Roentgenol. 2011;46:178–86.

    Article  PubMed  Google Scholar 

  3. Travis WD, Rekhtman N. Pathological diagnosis and classification of lung cancer in small biopsies and cytology: strategic management of tissue for molecular testing. Semin Respir Crit Care Med. 2011;32:22–31.

    Article  PubMed  Google Scholar 

  4. Nicholson AG, Gonzalez D, Shah P, Pynegar MJ, Deshmukh M, Rice A, et al. Refining the diagnosis and egfr status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, ttf-1, cytokeratin 5/6, and p63, and egfr mutation analysis. J Thorac Oncol. 2010;5:436–41.

    Article  PubMed  Google Scholar 

  5. Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol. 2013;31:992–1001.

    Article  CAS  PubMed  Google Scholar 

  6. Claiborne PM, Fowler CS, Vaporciyan AA. Follow-up of patients with resected thoracic malignancies. Thorac Surg Clin. 2012;22:123–31.

    Article  PubMed  Google Scholar 

  7. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, 2004. CA Cancer J Clin. 2004;54:8–29.

    Article  PubMed  Google Scholar 

  8. Li X, Lu J, Ren H, Chen T, Gao L, Di L, et al. Combining multiple serum biomarkers in tumor diagnosis: a clinical assessment. Mol Clin Oncol. 2013;1:153–60.

    PubMed  Google Scholar 

  9. Smith RA, Cokkinides V, Brooks D, Saslow D, Shah M, Brawley OW. Cancer screening in the United States, 2011: a review of current american cancer society guidelines and issues in cancer screening. CA cancer J Clin. 2011;61:8–30.

    Article  PubMed  Google Scholar 

  10. Chen HY, Xu CS, Jin QE, Liu ZH. S100 protein family in human cancer. Am J Cancer Res. 2014;4:89–115.

    PubMed  PubMed Central  Google Scholar 

  11. Stradal TB, Troxler H, Heizmann CW, Gimona M. Mapping the zinc ligands of s100a2 by site-directed mutagenesis. J Biol Chem. 2000;275:13219–27.

    Article  CAS  PubMed  Google Scholar 

  12. Nacken W, Roth J, Sorg C, Kerkhoff C. S100a9/s100a8: Myeloid representatives of the s100 protein family as prominent players in innate immunity. Microsc Res Tech. 2003;60:569–80.

    Article  CAS  PubMed  Google Scholar 

  13. Donato R. Intracellular and extracellular roles of s100 proteins. Microsc Res Tech. 2003;60:540–51.

    Article  CAS  PubMed  Google Scholar 

  14. Naz S, Bashir M, Ranganathan P, Bodapati P, Santosh V, Kondaiah P. Protumorigenic actions of s100a2 involve regulation of pi3/akt signaling and functional interaction with smad3. Carcinogenesis. 2014;35:14–23.

    Article  CAS  PubMed  Google Scholar 

  15. Bartling B, Rehbein G, Schmitt WD, Hofmann HS, Silber RE, Simm A. S100a2-s100p expression profile and diagnosis of non-small cell lung carcinoma: impairment by advanced tumour stages and neoadjuvant chemotherapy. Eur J Cancer. 2007;43:1935–43.

    Article  CAS  PubMed  Google Scholar 

  16. Emberley ED, Murphy LC, Watson PH. S100 proteins and their influence on pro-survival pathways in cancer. Biochem Cell Biol. 2004;82:508–15.

    Article  CAS  PubMed  Google Scholar 

  17. Mishra SK, Siddique HR, Saleem M. S100a4 calcium-binding protein is key player in tumor progression and metastasis: Preclinical and clinical evidence. Cancer Metastasis Rev. 2012;31:163–72.

    Article  CAS  PubMed  Google Scholar 

  18. Salama I, Malone PS, Mihaimeed F, Jones JL. A review of the s100 proteins in cancer. Eur J Surg Oncol. 2008;34:357–64.

    Article  CAS  PubMed  Google Scholar 

  19. Wicki R, Franz C, Scholl FA, Heizmann CW, Schafer BW. Repression of the candidate tumor suppressor gene s100a2 in breast cancer is mediated by site specific hypermethylation. Cell Calcium. 1997;22:243–54.

    Article  CAS  PubMed  Google Scholar 

  20. Wolf S, Haase-Kohn C, Pietzsch J. S100a2 in cancerogenesis: a friend or a foe? Amino Acids. 2011;41:849–61.

    Article  CAS  PubMed  Google Scholar 

  21. Bulk E, Sargin B, Krug U, Hascher A, Jun Y, Knop M, et al. S100a2 induces metastasis in non-small cell lung cancer. Clin Cancer Res. 2009;15:22–9.

    Article  CAS  PubMed  Google Scholar 

  22. Diederichs S, Bulk E, Steffen B, Ji P, Tickenbrock L, Lang K, et al. S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res. 2004;64:5564–9.

    Article  CAS  PubMed  Google Scholar 

  23. Ishii A, Suzuki M, Satomi K, Kobayashi H, Sakashita S, Kano J, et al. Increased cytoplasmic s100a6 expression is associated with pulmonary adenocarcinoma progression. Pathol Int. 2009;59:623–30.

    Article  CAS  PubMed  Google Scholar 

  24. De Petris L, Orre LM, Kanter L, Pernemalm M, Koyi H, Lewensohn R, et al. Tumor expression of s100a6 correlates with survival of patients with stage i non-small-cell lung cancer. Lung Cancer. 2009;63:410–7.

    Article  PubMed  Google Scholar 

  25. Melle C, Ernst G, Schimmel B, Bleul A, von Eggeling F. Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the ca(2+)-binding proteins s100a6 and s100a11. PLoS One. 2008;3:e3767.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mischke D, Korge BP, Marenholz I, Volz A, Ziegler A. Genes encoding structural proteins of epidermal cornification and s100 calcium-binding proteins form a gene complex (“epidermal differentiation complex”) on human chromosome 1q21. J Investig Dermatol. 1996;106:989–92.

    Article  CAS  PubMed  Google Scholar 

  27. Luu HH, Zhou L, Haydon RC, Deyrup AT, Montag AG, Huo D, et al. Increased expression of s100a6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma. Cancer Lett. 2005;229:135–48.

    Article  CAS  PubMed  Google Scholar 

  28. McKiernan E, McDermott EW, Evoy D, Crown J, Duffy MJ. The role of s100 genes in breast cancer progression. Tumor Biol. 2011;32:441–50.

    Article  CAS  Google Scholar 

  29. Nonaka D, Chiriboga L, Rubin BP. Differential expression of s100 protein subtypes in malignant melanoma, and benign and malignant peripheral nerve sheath tumors. J Cutan Pathol. 2008;35:1014–9.

    Article  PubMed  Google Scholar 

  30. Ohuchida K, Mizumoto K, Ishikawa N, Fujii K, Konomi H, Nagai E, et al. The role of s100a6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target. Clin Cancer Res. 2005;11:7785–93.

    Article  CAS  PubMed  Google Scholar 

  31. Slomnicki LP, Nawrot B, Legniak W. S100a6 binds p53 and affects its activity. Int J Biochem Cell Biol. 2009;41:784–90.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by National Natural Science Foundation of China (No. 81302029), Natural Science Foundation of Shaanxi Province of China (No. 2014JQ4149), Fundamental Research Funds for the Central Universities in Xi’an Jiaotong University (No. xjj2015086), and China Postdoctoral Science Foundation (No. 2015 M570841).

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Mingwei Chen or Hui Ren.

Additional information

Ting Wang and Yiqian Liang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, T., Liang, Y., Thakur, A. et al. Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non-small cell lung cancer. Tumor Biol. 37, 2299–2304 (2016). https://doi.org/10.1007/s13277-015-4057-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4057-z

Keywords

Navigation