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Quantitative analysis of promoter methylation of the EDNRB gene in gastric cancer

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Abstract

Hypermethylation has been shown in the promoter region of the endothelin receptor B (EDNRB) gene in several human tumors. However, its role in gastric cancer formation is still unclear. In this study, the methylation status of the EDNRB gene in paired gastric cancer tissues and adjacent normal tissues from 96 patients was detected quantitatively using pyrosequencing. The results showed the methylation of promoter of EDNRB gene in gastric cancer (50.42 ± 9.03%) was significantly higher than in adjacent normal tissues (6.47 ± 2.98%) (P < 0.01). Among 96 tumor tissues, promoter hypermethylation of the EDNRB gene was correlated with tumor infiltration (T1: 47.4 ± 7.31% T2:48.2 ± 9.17% T3:52.9 ± 6.48% T4:53.2 ± 10.45%), lymph node metastasis (N0:45.4 ± 6.99% N1:49.0 ± 9.10% N2:52.0 ± 8.40% N3:53.7 ± 9.92%), and distant metastasis (M0:48.9 ± 6.99% M1:53.9 ± 11.98%) (P < 0.05), but it was not associated with other clinicopathological characteristics. In addition, the treatment of the human gastric cancer cell line, SGC-7901, with demethylation agent can restore the expression of EDNRB. Our results suggest that promoter hypermethylation of EDNRB gene is highly prevalent in gastric cancer, which may play a role in the pathogenesis of gastric cancer. Futhermore, hypermethylation of EDNRB gene was remarkably related to infiltration and metastasis of gastric cancer and may attribute to the tumor progression.

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References

  1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002 CA Cancer. J Clin. 2005;55(2):74–108.

    Google Scholar 

  2. Yu M, Zheng HC, Xia P, Takahashi H, Masuda S. Takano Y and Xu HM: Comparison in pathological behaviours & prognosis of gastric cancers from general hospitals between China & Japan. Indian J Med Res. 2010;132:295–302.

    PubMed  Google Scholar 

  3. Jones PA, Takai D. The role of DNA methylation in mammalian epigenetics. Science. 2001;293:1068–70.

    Article  PubMed  CAS  Google Scholar 

  4. Esteller M. Relevance of DNA methylation in the management of cancer. Lancet Oncol. 2003;4:351–8.

    Article  PubMed  CAS  Google Scholar 

  5. Kikuchi R, Tsuda H, Kanai Y, et al. Promoter hypermethylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer. Cancer Res. 2007;67:7095–105.

    Article  PubMed  CAS  Google Scholar 

  6. Issa JP. CpG island methylation phenotype in cancer. Nat Rev Cancer. 2004;4:988–93.

    Article  PubMed  CAS  Google Scholar 

  7. Baylin SB, Herman JR, Graff JR, Vertino PM, Issa JP. Alterations in DNA methylation : a fundamental aspect of neoplasia. Adv Cancer Res. 1998;72:141–96.

    Article  PubMed  CAS  Google Scholar 

  8. Fleisher AS, Esteller M, Wang S, et al. Hypermethylation of the hMLH1 gene promoter in human gastric cancers with microsatellite instability. Cancer Res. 1999;59:1090–5.

    PubMed  CAS  Google Scholar 

  9. Machado JC, Oliveira C, Carvalho R, et al. E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncology. 2001;20:1525–8.

    CAS  Google Scholar 

  10. Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001;61(8):3225–9.

    PubMed  CAS  Google Scholar 

  11. Buffart TE, Overmeer RM, Steenbergen RD, et al. MAL promoter hypermethylation as a novel prognostic marker in gastric cancer. Br J Cancer. 2008;99:1802–7.

    Article  PubMed  CAS  Google Scholar 

  12. Pla P, Larue L. Involvement of endothelin receptors in normal and pathological development of neural crest cells. Int J Dev Biol. 2003;47:315–25.

    PubMed  CAS  Google Scholar 

  13. Puffenberger EG, Hosoda K, Washington SS, et al. A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung’s disease. Cell. 1994;79:1257–66.

    Article  PubMed  CAS  Google Scholar 

  14. Pao MM, Tsutsumi M, Liang G, et al. The endothelin receptor B promoter displays heterogenous, site special methylation patterns in normal and tumor cells. Hum Mol Genet. 2001;10:903–10.

    Article  PubMed  CAS  Google Scholar 

  15. Yang AS, Doshi KD, Choi SW, et al. DNA methylation changes after 5-aza-2′-deoxycytidine therapy in patients with leukemia. Cancer Res. 2006;66(10):5495–503.

    Article  PubMed  CAS  Google Scholar 

  16. Lo KW, Tsang YS, Kwong J, et al. Promoter hypermethylation of the EDNRB gene in nasopharyngeal carcinoma. Int J Cancer. 2002;98:651–5.

    Article  PubMed  CAS  Google Scholar 

  17. Jeronimo C, Henrique R, Campos PF, et al. Endothelin B receptor gene hypermethylation in prostate adenocarcinoma. J Clin Patho. 2003;56:52–5.

    Article  CAS  Google Scholar 

  18. Eberle J, Weitmann S, Thieck O, et al. Downregulation of endothelin B receptor in human melanoma cell lines parallel to differentiation genes. J Invest Dermoatol. 1999;112:925–32.

    Article  CAS  Google Scholar 

  19. Chen SC, Lin CY, Chen YH, et al. Aberrant promoter methylation of EDNRB in lung cancer in Taiwan. Oncol Rep. 2006;15:167–82.

    PubMed  Google Scholar 

  20. Zhao BJ, Sun DG, Zhang M, et al. Identification of aberrant promoter methylation of EDNRB gene in esophageal squamous cell carcinoma. Dis Esophagus. 2009;22(1):55–61.

    Article  PubMed  Google Scholar 

  21. Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nature Rev. 2006;7:21–33.

    Article  CAS  Google Scholar 

  22. Ushijima T. Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer. 2005;5:223–31.

    Article  PubMed  CAS  Google Scholar 

  23. Hsu LS, Lee HC, Chau GY, et al. Aberrant methylation of EDNRB and p16 genes in hepatocellular carcinoma (HCC) in Taiwan. Oncol Rep. 2006;15:507–11.

    PubMed  CAS  Google Scholar 

  24. Pflug BR, Zheng H, Udan MS, et al. Endothelin-1 promotes cell survival in renal cell carcinoma through the ET(A) receptor. Cancer Lett. 2007;246:139–48.

    Article  PubMed  CAS  Google Scholar 

  25. Jha AK, Nikbakht M, Parashar G, et al. Reversal of hypermethylation and reactivation of the rarβ2 gene by natural compounds in cervical cancer cell lines. Folia Biol (Praha). 2010;56(5):195–200.

    CAS  Google Scholar 

  26. Yegnasubramanian S, Kowalski J, Gonzalgo ML, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004;64:1975–86.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30872473).

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Correspondence to Guobin Wang.

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Tao, K., Wu, C., Wu, K. et al. Quantitative analysis of promoter methylation of the EDNRB gene in gastric cancer. Med Oncol 29, 107–112 (2012). https://doi.org/10.1007/s12032-010-9805-8

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  • DOI: https://doi.org/10.1007/s12032-010-9805-8

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