Skip to main content

Advertisement

SpringerLink
Log in

Quantitative proteomic analysis identifying three annexins as lymph node metastasis-related proteins in lung adenocarcinoma

  • Original paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Lymph node status is a strong predictor of outcome for lung adenocarcinoma (AdC) patients. To explore novel potential protein markers for predicting lymph node metastasis of lung AdC, differential proteomic analysis on microdissected cancer cells from primary lung AdC and matched lymph node (LN) metastatic tissues by laser capture microdissection (LCM) was conducted using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Annexins including annexin-1, annexin-2 and annexin-3 were identified and found to be overexpressed in matched LN metastatic tissues compared to primary lung AdC. Furthermore, differential expression levels of the three annexins were evaluated in paraffin-embedded 188 primary lung AdC tissues and 65 matched positive lymph node specimens using immunohistochemistry. High expression of annexin-1, annexin-2, and annexin-3 was all frequently observed in matched positive lymph node tissues compared to primary lung AdC. In primary lung AdC, expression levels of the three annexins in primary lymph node-positive AdC tissues were higher than primary lymph node-negative AdC tissues. Multivariate logistic regression analysis indicated annexin-1, annexin-2, and annexin-3 were all significant risk factors for lymph node metastasis. Furthermore, statistical analysis indicated that the concomitant expression of annexin-1/annexin-2, annexin-1/annexin-3, or annexin-2/annexin-3 and combined expression of all three markers had stronger correlation with lymph node metastasis. Our results suggest that annexin-1, annexin-2, and annexin-3 are identified as potential biomarkers associated with lymph node metastasis in lung AdC.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Little AG, et al. National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care. Lung Cancer. 2007;57(3):253–60.

    Article  PubMed  Google Scholar 

  2. Liao ML, et al. Incidence, time trend, survival, and predictive factors of lung cancer in Shanghai populations. Zhonghua Yi Xue Za Zhi. 2007;87(27):1876–80.

    PubMed  Google Scholar 

  3. Jemal A, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106–30.

    Article  PubMed  Google Scholar 

  4. Giese A, et al. Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol. 2003;21(8):1624–36.

    Article  PubMed  CAS  Google Scholar 

  5. Yoshida BA, et al. Metastasis-suppressor genes: a review and perspective on an emerging field. J Natl Cancer Inst. 2000;92(21):1717–30.

    Article  PubMed  CAS  Google Scholar 

  6. Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer. 1997;80(8 Suppl):1529–37.

    Article  PubMed  CAS  Google Scholar 

  7. Van den Bergh G, Arckens L. Fluorescent two-dimensional difference gel electrophoresis unveils the potential of gel-based proteomics. Curr Opin Biotechnol. 2004;15(1):38–43.

    Article  PubMed  Google Scholar 

  8. Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev. 2002;82(2):331–71.

    PubMed  CAS  Google Scholar 

  9. Rescher U, Gerke V. Annexins—unique membrane binding proteins with diverse functions. J Cell Sci. 2004;117(Pt 13):2631–9.

    Article  PubMed  CAS  Google Scholar 

  10. Cheng AL, et al. Identificating cathepsin D as a biomarker for differentiation and prognosis of nasopharyngeal carcinoma by laser capture microdissection and proteomic analysis. J Proteome Res. 2008;7(6):2415–26.

    Article  PubMed  CAS  Google Scholar 

  11. Yang YX, et al. Proteome analysis of multidrug resistance in vincristine-resistant human gastric cancer cell line SGC7901/VCR. Proteomics. 2006;6(6):2009–21.

    Article  PubMed  CAS  Google Scholar 

  12. Yang F, et al. Identification of tumor antigens in human lung squamous carcinoma by serological proteome analysis. J Proteome Res. 2007;6(2):751–8.

    Article  PubMed  CAS  Google Scholar 

  13. Cheng A-L et al. Identification of novel nasopharyngeal carcinoma biomarkers by laser capture microdissection and proteomic analysis. Clin Cancer Res 2008;14(2):435–5.

    Google Scholar 

  14. Mai J, et al. Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. J Biol Chem. 2000;275(17):12806–12.

    Article  PubMed  CAS  Google Scholar 

  15. Lim LH, Pervaiz S. Annexin 1: the new face of an old molecule. Faseb J. 2007;21(4):968–75.

    Article  PubMed  CAS  Google Scholar 

  16. Chiang Y, et al. Specific down-regulation of annexin II expression in human cells interferes with cell proliferation. Mol Cell Biochem. 1999;199(1–2):139–47.

    Article  PubMed  CAS  Google Scholar 

  17. Cole SP, et al. Elevated expression of annexin II (lipocortin II, p36) in a multidrug resistant small cell lung cancer cell line. Br J Cancer. 1992;65(4):498–502.

    Article  PubMed  CAS  Google Scholar 

  18. Emoto K, et al. Annexin II overexpression correlates with stromal tenascin-C overexpression: a prognostic marker in colorectal carcinoma. Cancer. 2001;92(6):1419–26.

    Article  PubMed  CAS  Google Scholar 

  19. Wang KL, et al. Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Clin Cancer Res. 2006;12(15):4598–604.

    Article  PubMed  CAS  Google Scholar 

  20. Babbin BA, et al. Annexin I regulates SKCO-15 cell invasion by signaling through formyl peptide receptors. J Biol Chem. 2006;281(28):19588–99.

    Article  PubMed  CAS  Google Scholar 

  21. Liang L, Qu L, Ding Y. Protein and mRNA characterization in human colorectal carcinoma cell lines with different metastatic potentials. Cancer Invest. 2007;25(6):427–34.

    Article  PubMed  CAS  Google Scholar 

  22. Dai Z, et al. Identification and analysis of altered alpha1, 6-fucosylated glycoproteins associated with hepatocellular carcinoma metastasis. Proteomics. 2006;6(21):5857–67.

    Article  PubMed  CAS  Google Scholar 

  23. Wang KL, et al. Expression of annexin A1 in esophageal and esophagogastric junction adenocarcinomas: association with poor outcome. Clin Cancer Res. 2006;12(15):4598–604.

    Article  PubMed  CAS  Google Scholar 

  24. Chen ZG. Exploration of metastasis-related proteins as biomarkers and therapeutic targets in the treatment of head and neck cancer. Curr Cancer Drug Targets. 2007;7(7):613–22.

    Article  PubMed  CAS  Google Scholar 

  25. Vishwanatha JK, et al. Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis. 1993;14(12):2575–9.

    Article  PubMed  CAS  Google Scholar 

  26. Tanaka T, et al. Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis. Oncogene. 2004;23(22):3980–9.

    Article  PubMed  CAS  Google Scholar 

  27. Vellucci VF, Germino, FJ Reiss M. Cloning of putative growth regulatory genes from primary human keratinocytes by subtractive hybridization. Gene 1995;166(2):213–20.

    Google Scholar 

  28. Semov A, et al. Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation. J Biol Chem. 2005;280(21):20833–41.

    Article  PubMed  CAS  Google Scholar 

  29. Harashima M, et al. Annexin A3 expression increases in hepatocytes and is regulated by hepatocyte growth factor in rat liver regeneration. J Biochem. 2008;143(4):537–45.

    Article  PubMed  CAS  Google Scholar 

  30. Madoz-Gurpide J, et al. Proteomics-based validation of genomic data: applications in colorectal cancer diagnosis. Mol Cell Proteomics. 2006;5(8):1471–83.

    Article  PubMed  CAS  Google Scholar 

  31. Park JE, et al. Annexin A3 is a potential angiogenic mediator. Biochem Biophys Res Commun. 2005;337(4):1283–7.

    Article  PubMed  CAS  Google Scholar 

  32. Yao H, et al. Identification of metastasis associated proteins in human lung squamous carcinoma using two-dimensional difference gel electrophoresis and laser capture microdissection. Lung Cancer. 2009;65(1):41–8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from National Key Basic Research Program of China (2001CB510207), the Fundamental Research Funds for the Central Universities (2010121104), Outstanding Scholars of New Era from Ministry of Education of China (2002-48), key research program from Science and Technology Committee of Hunan, China (04XK1001-1, 05SK1004-1), and key research program from Public Health Bureau of Hunan Province, China (Z02-04).

Conflicts of interest

No conflicts of interest are declared.

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian, People’s Republic of China

    Ying-Fu Liu

  2. Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87# Xiangya Road, 410008, Changsha, Hunan, People’s Republic of China

    Ying-Fu Liu, Mao-Yu Li, Peng-Fei Zhang, Fang Peng, Guo-Qing Li, Zhi-Qiang Xiao & Zhu-Chu Chen

  3. Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China

    Zhu-Chu Chen

  4. Molecular and Computational Biology, University of Southern California, Los Angeles, CA, USA

    Yong-Heng Chen

Authors
  1. Ying-Fu Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong-Heng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mao-Yu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng-Fei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fang Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guo-Qing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhi-Qiang Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhu-Chu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhu-Chu Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, YF., Chen, YH., Li, MY. et al. Quantitative proteomic analysis identifying three annexins as lymph node metastasis-related proteins in lung adenocarcinoma. Med Oncol 29, 174–184 (2012). https://doi.org/10.1007/s12032-010-9761-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9761-3

Keywords

Search

Navigation