Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical Outcomes of Downregulation of E-cadherin Gene Expression in Non-small Cell Lung Cancer

  • Zheng, Shi-Ying (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University) ;
  • Hou, Jing-Yu (The First Affiliated Hospital of Xinxiang Medical University) ;
  • Zhao, Jun (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University) ;
  • Jiang, Dong (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University) ;
  • Ge, Jin-Feng (Department of Cardio-thoracic Surgery, the First Affiliated Hospital of Soochow University) ;
  • Chen, Sheng (Huaian No.1 People's Hospital, Nanjing Medical University)
  • Published : 2012.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer (NSCLC) and its association with clinical pathological parameters, and to explore the relationship between downregulation of E-cadherin gene expression and the methylation status of its promoter region. Methods: Nested methylation-specific PCR was performed to examine CpG methylation within the 5' CpG island of the E-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lung cancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Results: Of thirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the 12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayed reduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA was unavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene. Conclusion: These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of NSCLC.

Keywords

References

  1. Alves CC, Carneiro F, Hoefler H, et al (2009). Role of the epithelialmesenchymal transition regulator Slug in primary human cancers. Front Biosci, 14, 3035-50.
  2. Berx G, Becker KF, Hofler H, et al (1998). Mutations of the human E-cadherin (CDH1) gene. Hum Mutat, 12, 226-37. https://doi.org/10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D
  3. Birchmeier W, Behrens J (1994). Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta, 1198, 11-26.
  4. Chen CL, Liu SS, Ip SM, et al (2003). E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours. Eur J Cancer, 39, 517-23. https://doi.org/10.1016/S0959-8049(02)00175-2
  5. Cheng CW, Wu PE, Yu JC, et al (2001). Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene, 20, 3814-23. https://doi.org/10.1038/sj.onc.1204505
  6. Corn PG, Heath EI, Heitmiller R, et al (2001). Frequent hypermethylation of the 5' CpG island of E-cadherin in esophageal adenocarcinoma. Clin Cancer Res, 7, 2765-9.
  7. Esteller M (2002). The coming of age of DNA methylation in medicine in the genomics and postgenomics era. Clin Immunol, 103, 213-6. https://doi.org/10.1006/clim.2002.5216
  8. Fei QY, Zhang HT, Chen XF, et al (2002). Defected expression of E-cadherin in non-small cell lung cancer. Lung Cancer, 37, 142-52.
  9. Gamallo C, Palacios J, Suarez A, et al (1993). Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol, 142, 987-93.
  10. Graff JR, Herman JG, Lapidus RG, et al (1995). E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res, 55, 5195-9.
  11. Guarino M (2007). Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol, 12, 2153-60.
  12. Herman JG, Graff JR, Myohanen S, et al (1996). Methylationspecific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA, 93, 9821-6. https://doi.org/10.1073/pnas.93.18.9821
  13. Hirohashi S (1998). Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol, 153, 333-9. https://doi.org/10.1016/S0002-9440(10)65575-7
  14. Hiraguri S, Godfrey T, Nakamura H, et al (1998). Mechanisms of inactivation of E-cadherin in breast cancer cell lines. Cancer Res, 58, 1972-7.
  15. Kanai Y, Ushijima S, Hui AM, et al (1997). The E-cadherin gene is silenced by CpG methylation in human hepatocellular carcinomas. Int J Cancer, 71, 355-9. https://doi.org/10.1002/(SICI)1097-0215(19970502)71:3<355::AID-IJC8>3.0.CO;2-X
  16. Kase S, Sugio K, Yamazaki K, et al (2000). Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res, 6, 4789-96.
  17. Leonhardt H, Cardoso MC (2000). DNA methylation, nuclear structure, gene expression and cancer. J Cell Biochem, 35, 78-83.
  18. Li LC. Zhao H. Nakajima K, et al (2001). Methylation of the E-cadherin gene promoter correlates with progression of prostate cancer. J Urol, 166, 705-9. https://doi.org/10.1016/S0022-5347(05)66047-8
  19. Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T) Method. Methods, 25, 402-8. https://doi.org/10.1006/meth.2001.1262
  20. Machado JC, Oliveira C, Carvalho R, et al (2001). E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene, 20, 1525-8. https://doi.org/10.1038/sj.onc.1204234
  21. Margineanu E, Cotrutz CE, Cotrutz C (2008). Correlation between E-cadherin abnormal expressions in different types of cancer and the process of metastasis. Rev Med Chir Soc Med Nat Iasi, 112, 432-6.
  22. Mountain CF (1997). Revisions in the international system for staging lung cancer. Chest, 111, 1710-7. https://doi.org/10.1378/chest.111.6.1710
  23. Oka H, Shiozaki H, Kobayashi K, et al (1993). Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res, 53, 1696-701.
  24. Schipper JH, Frixen UH, Behrens J, et al (1991). E-cadherin expression in squamous cell carcinomas of head and neck: Inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res, 51, 6328-37.
  25. Shimoyama Y, Hirohashi S (1991). Cadherin intercellular adhesion molecule in hepatocellular carcinomas: Loss of E-cadherin expression in an undifferentiated carcinoma. Cancer Lett, 57, 131-5. https://doi.org/10.1016/0304-3835(91)90206-W
  26. Shimoyama Y, Hirohashi S (1991). Expression of E- and P-cadherin in gastric carcinomas. Cancer Res, 51, 2185-92.
  27. Shiozaki H, Tahara H, Oka H, et al (1991). Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am J Pathol, 139, 17-23.
  28. Tamura G, Yin J, Wang S, et al (2000). E-cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst, 92, 569-73. https://doi.org/10.1093/jnci/92.7.569
  29. Tamura G, Yin J, Wang S, et al (2000). E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J Natl Cancer Inst (Bethesda), 92, 569-73.
  30. Tsao SW, Liu Y, Wang X, et al (2003). The association of E-cadherin expression and the methylation status of the E-cadherin gene in nasopharyngeal carcinoma cells. Eur J Cancer, 39, 524-31. https://doi.org/10.1016/S0959-8049(02)00494-X
  31. Yoshiura K, Kanai Y, Ochiai A, et al (1995). Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci USA, 9, 7416-9.
  32. Zhang HT, Chen XF, Wang MH, et al (2004). Defective expression of transforming growth factor beta receptor type II is associated with CpG methylated promoter in primary non-small cell lung cancer. Clin Cancer Res, 10, 2359-67. https://doi.org/10.1158/1078-0432.CCR-0959-3
  33. Zochbauer-Muller S, Fong KM, Virmani AK, et al (2001). Aberrant promoter methylation of multiple genes in non-small cell lung cancers. Cancer Res. 2001 Jan 1;61(1):249-55.

Cited by

  1. Loss of Expression and Aberrant Methylation of the CDH1 (E-cadherin) Gene in Breast Cancer Patients from Kashmir vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6397
  2. E-cadherin gene methylation in lung cancer vol.35, pp.9, 2014, https://doi.org/10.1007/s13277-014-2076-9
  3. The clinicopathological significance and potential drug target of E-cadherin in NSCLC vol.36, pp.8, 2015, https://doi.org/10.1007/s13277-015-3298-1
  4. gene increase the risk of lung cancer? A meta-analysis pp.17597706, 2018, https://doi.org/10.1111/1759-7714.12900