Advertisement

Tumor Biology

, Volume 35, Issue 7, pp 6649–6656 | Cite as

Role of EZH2 protein expression in gastric carcinogenesis among Asians: a meta-analysis

  • Lin Guo
  • Teng-Fei Yang
  • Shi-Chao Liang
  • Ji-Xiang Guo
  • Qiang Wang
Research Article

Abstract

The present meta-analysis aggregated the results of relevant studies to identify the role of zeste homolog 2 (EZH2) expression in gastric carcinogenesis among Asians. Related articles were found by searching the following electronic databases without language restrictions: PubMed, SpringerLink, Karger Medical and Scientific Publishers, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Google Scholar. Meta-analysis was performed using STATA statistical software. Crude odds ratios (ORs) or hazard ratios (HRs) with their corresponding 95 % confidence interval (95 % CI) were calculated. Ten relevant studies, which enrolled a total of 872 gastric cancer patients, were selected for statistical analysis. The most important findings of our meta-analysis was that cancer tissues exhibited higher expression levels of EZH2 protein than normal, adjacent and benign tissues (cancer tissues vs normal tissues: OR = 32.15, 95 % CI 22.58 ~ 45.79, P < 0.001; cancer tissues vs adjacent tissues: OR = 16.10, 95 % CI 11.35 ~ 22.84, P < 0.001; cancer tissues vs benign tissues: OR = 2.66, 95 % CI 1.89 ~ 3.75, P < 0.001; respectively). Furthermore, we observed positive correlations between EZH2 expression and the TNM stage (OR = 2.86, 95 % CI 1.72 ~ 4.75, P < 0.001) as well as lymph node metastasis (OR = 3.02, 95 % CI 2.01 ~ 4.53, P < 0.001) of patients with gastric carcinoma. The correlation between EZH2 expression and gastric cancer prognosis was also evaluated in the meta-analysis. Statistical analysis demonstrated that the overall survival (OS) of EZH2-negative patients was shorter than that of patients with positive expressions of EZH2 (HR = 0.54, 95 % CI = 0.05 ~ 1.03, P = 0.032). Our meta-analysis confirmed the view that EZH2 expression might participate in the development of gastric carcinogenesis. Thus, EZH2 protein may be a valuable biomarker for the diagnosis and prognosis of gastric cancer.

Keywords

Enhancer of zeste homolog 2 Gastric cancer Carcinogenesis Meta-analysis 

Notes

Acknowledgments

We would like to acknowledge the reviewers for their helpful comments on this paper.

Conflicts of interest

None

References

  1. 1.
    Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer. 2010;127(12):2893–917.CrossRefPubMedGoogle Scholar
  2. 2.
    Nagini S. Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012;4(7):156–69.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMedGoogle Scholar
  4. 4.
    Krejs GJ. Gastric cancer: epidemiology and risk factors. Dig Dis. 2010;28(4–5):600–3.CrossRefPubMedGoogle Scholar
  5. 5.
    Brenner H, Rothenbacher D, Arndt V. Epidemiology of stomach cancer. Methods Mol Biol. 2009;472:467–77.CrossRefPubMedGoogle Scholar
  6. 6.
    Milne AN, Carneiro F, O'Morain C, Offerhaus GJ. Nature meets nurture: molecular genetics of gastric cancer. Hum Genet. 2009;126(5):615–28.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Wang C, Liu X, Chen Z, Huang H, Jin Y, Kolokythas A, et al. Polycomb group protein EZH2-mediated E-cadherin repression promotes metastasis of oral tongue squamous cell carcinoma. Mol Carcinog. 2013;52(3):229–36.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Fujii S, Ito K, Ito Y, Ochiai A. Enhancer of zeste homologue 2 (EZH2) down-regulates runx3 by increasing histone H3 methylation. J Biol Chem. 2008;283(25):17324–32.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Lee H, Yoon SO, Jeong WY, Kim HK, Kim A, Kim BH. Immunohistochemical analysis of polycomb group protein expression in advanced gastric cancer. Hum Pathol. 2012;43(10):1704–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Xiao Y. Enhancer of zeste homolog 2: a potential target for tumor therapy. Int J Biochem Cell Biol. 2011;43(4):474–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Chase A, Cross NC. Aberrations of ezh2 in cancer. Clin Cancer Res. 2011;17(9):2613–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Choi JH, Song YS, Yoon JS, Song KW, Lee YY. Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and metastasis in gastric cancer. APMIS. 2010;118(3):196–202.CrossRefPubMedGoogle Scholar
  13. 13.
    He LJ, Cai MY, Xu GL, Li JJ, Weng ZJ, Xu DZ, et al. Prognostic significance of overexpression of EZH2 and H3K27ME3 proteins in gastric cancer. Asian Pac J Cancer Prev. 2012;13(7):3173–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhao SF, Yu DH. Correlation between EZH2 protein in gastric carcinoma and helicobacter pylori l-form infection. Chin J Histochem Cytochem. 2013;22(3):224–9.Google Scholar
  15. 15.
    Stang A. Critical evaluation of the newcastle-ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25(9):603–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Zintzaras E, Ioannidis JP. Hegesma: genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005;21(18):3672–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676–80.CrossRefPubMedGoogle Scholar
  18. 18.
    Gao F, Lv Y, Zhu Y, Chen M, Shen S, Cao J, et al. Correlation of epigenetic aberrance with stat3 signaling pathway in gastric carcinogenesis. Dig Dis Sci. 2012;57(8):2055–62.CrossRefPubMedGoogle Scholar
  19. 19.
    Lin GH, Zhang SY, Li LQ, Li YP. The expression and clinical significance of EZH2 gene in gastric carcinoma. Guangdong Med J. 2011;32(24):3233–5.Google Scholar
  20. 20.
    Cai GH, Wang K, Miao Q, Peng YS, Chen XY. Expression and clinical significance of polycomb group protein EZH2 in the carcinogenesis and progression of gastric cancer. Chin J Gastroenterol. 2010;15(6):339–43.Google Scholar
  21. 21.
    Miao F, Li JS. Representation and significance of EZH2, Ki-67 in gastric carcinoma. J Taishan Med Col. 2008;29(2):87–9.Google Scholar
  22. 22.
    Matsukawa Y, Semba S, Kato H, Ito A, Yanagihara K, Yokozaki H. Expression of the enhancer of zeste homolog 2 is correlated with poor prognosis in human gastric cancer. Cancer Sci. 2006;97(6):484–91.CrossRefPubMedGoogle Scholar
  23. 23.
    Fujii S, Ochiai A. Enhancer of zeste homolog 2 downregulates E-cadherin by mediating histone H3 methylation in gastric cancer cells. Cancer Sci. 2008;99(4):738–46.CrossRefPubMedGoogle Scholar
  24. 24.
    Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K. Ezh2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J. 2003;22(20):5323–35.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Alajez NM, Shi W, Hui AB, Bruce J, Lenarduzzi M, Ito E, et al. Enhancer of zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98. Cell Death Dis. 2010;1:e85.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Hinz S, Weikert S, Magheli A, Hoffmann M, Engers R, Miller K, et al. Expression profile of the polycomb group protein enhancer of zeste homologue 2 and its prognostic relevance in renal cell carcinoma. J Urol. 2009;182(6):2920–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Cao Q, Yu J, Dhanasekaran SM, Kim JH, Mani RS, Tomlins SA, et al. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008;27(58):7274–84.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Tonini T, D'Andrilli G, Fucito A, Gaspa L, Bagella L. Importance of EZH2 polycomb protein in tumorigenesis process interfering with the pathway of growth suppressive key elements. J Cell Physiol. 2008;214(2):295–300.CrossRefPubMedGoogle Scholar
  29. 29.
    Lu H, Sun J, Wang F, Feng L, Ma Y, Shen Q, et al. Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC finger protein 4. Cell Death Dis. 2013;4:e776.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Lin Guo
    • 1
  • Teng-Fei Yang
    • 1
  • Shi-Chao Liang
    • 1
  • Ji-Xiang Guo
    • 1
  • Qiang Wang
    • 1
  1. 1.Department of Gastrointestinal and Nutriology SurgeryShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China

Personalised recommendations