Skip to main content

Advertisement

SpringerLink
Log in

Promoter methylation of H-cadherin is a potential biomarker in patients with bladder transitional cell carcinoma

  • Urology – Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Objectives

H-cadherin, functions as a tumor suppressor, is frequently silenced by promoter methylation in human cancers. The aim of this study was to evaluate the feasibility of using H-cadherin methylation in tumor tissues as a potential biomarker in patients with bladder transitional cell carcinoma (TCC).

Materials and methods

We examined the methylation status of H-cadherin in 133 primary bladder TCC samples and 43 normal bladder epithelial tissues using methylation-specific polymerase chain reaction (MSP) and then analyzed the associations between H-cadherin methylation and clinicopathologic features as well as patients’ outcome.

Results

H-cadherin methylation was detected in 47 (35.3%) bladder TCC samples, but not found in controls (P = 0.0000). Moreover, H-cadherin methylation was significantly associated with advanced stage (P = 0.0006), high grade (P = 0.0165), larger tumor size (P = 0.0225), tumor recurrence (P = 0.0106), and poor prognosis (P = 0.0000). In addition, multivariate analysis indicated that H-cadherin methylation is independently associated with poor outcome and had a relative risk of death of 3.832 (P = 0.0071, 95% confidence interval: 1.443–10.176).

Conclusions

The results suggest that H-cadherin methylation may be used as a potential biomarker for the malignancy of bladder TCC and as an independent prognostic biomarker in patients with bladder TCC.

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
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Van Rhijn BW, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, Witjes JA, Zlotta AR (2009) Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol 56:430–442

    Article  PubMed  Google Scholar 

  2. Ploeg M, Aben KK, Kiemeney LA (2009) The present and future burden of urinary bladder cancer in the world. World J Urol 27:289–293

    Article  PubMed  Google Scholar 

  3. Jacobs BL, Lee CT, Montie JE (2010) Bladder cancer in 2010: how far have we come? CA Cancer J Clin 60:244–272

    Article  PubMed  Google Scholar 

  4. Rübben H, Lutzeyer W, Fischer N, Deutz F, Lagrange W, Giani G (1988) Natural history and treatment of low and high risk superficial bladder tumors. J Urol 139:283–285

    PubMed  Google Scholar 

  5. Black PC, Dinney CP (2007) Bladder cancer angiogenesis and metastasis–translation from murine model to clinical trial. Cancer Metastasis Rev 26:623–634

    Article  PubMed  Google Scholar 

  6. Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, Amiel GE, Vazina A, Gupta A, Bastian PJ, Sagalowsky AI, Schoenberg MP, Lerner SP (2006) Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 176:2414–2422

    Article  PubMed  Google Scholar 

  7. Herr HW, Dotan Z, Donat SM, Bajorin DF (2007) Defining optimal therapy for muscle invasive bladder cancer. J Urol 177:437–443

    Article  PubMed  CAS  Google Scholar 

  8. Morgan TM, Clark PE (2010) Bladder cancer. Curr Opin Oncol 22:242–249

    Article  PubMed  Google Scholar 

  9. Andreeva AV, Kutuzov MA (2010) Cadherin 13 in cancer. Genes Chromosomes Cancer 49:775–790

    PubMed  CAS  Google Scholar 

  10. Jin Z, Cheng Y, Olaru A, Kan T, Yang J, Paun B, Ito T, Hamilton JP, David S, Agarwal R, Selaru FM, Sato F, Abraham JM, Beer DG, Mori Y, Shimada Y, Meltzer SJ (2008) Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors. Int J Cancer 123:2331–2336

    Article  PubMed  CAS  Google Scholar 

  11. Kim DS, Kim MJ, Lee JY, Kim YZ, Kim EJ, Park JY (2007) Aberrant methylation of E-cadherin and H-cadherin genes in nonsmall cell lung cancer and its relation to clinicopathologic features. Cancer 110:2785–2792

    Article  PubMed  CAS  Google Scholar 

  12. Dehan P, Kustermans G, Guenin S, Horion J, Boniver J, Delvenne P (2009) DNA methylation and cancer diagnosis: new methods and applications. Expert Rev Mol Diagn 9:651–657

    Article  PubMed  CAS  Google Scholar 

  13. Esteller M, Corn PG, Baylin SB, Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Res 61:3225–3229

    PubMed  CAS  Google Scholar 

  14. Kim YK, Kim WJ (2009) Epigenetic markers as promising prognosticators for bladder cancer. Int J Urol 16:17–22

    Article  PubMed  Google Scholar 

  15. Enokida H, Nakagawa M (2008) Epigenetics in bladder cancer. Int J Clin Oncol 13:298–307

    Article  PubMed  CAS  Google Scholar 

  16. Maruyama R, Toyooka S, Toyooka KO, Harada K, Virmani AK, Zöchbauer-Müller S, Farinas AJ, Vakar-Lopez F, Minna JD, Sagalowsky A, Czerniak B, Gazdar AF (2001) Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res 61:8659–8663

    PubMed  CAS  Google Scholar 

  17. Yu J, Zhu T, Wang Z, Zhang H, Qian Z, Xu H, Gao B, Wang W, Gu L, Meng J, Wang J, Feng X, Li Y, Yao X, Zhu J (2007) A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer. Clin Cancer Res 13:7296–7304

    Article  PubMed  CAS  Google Scholar 

  18. Oosterlinck W, Lobel B, Jakse G, Malmström PU, Stöckle M, Sternberg C (2002) Guidelines on bladder cancer. Eur Urol 41:105–112

    Article  PubMed  Google Scholar 

  19. Qian ZR, Sano T, Yoshimoto K, Asa SL, Yamada S, Mizusawa N, Kudo E (2007) Tumor-specific downregulation and methylation of the CDH13 (H-cadherin) and CDH1 (E-cadherin) genes correlate with aggressiveness of human pituitary adenomas. Mod Pathol 20:1269–1277

    Article  PubMed  CAS  Google Scholar 

  20. Kim JS, Han J, Shim YM, Park J, Kim DH (2005) Aberrant methylation of H-cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma. Cancer 104:1825–1833

    Article  PubMed  CAS  Google Scholar 

  21. Sakai M, Hibi K, Koshikawa K, Inoue S, Takeda S, Kaneko T, Nakao A (2004) Frequent promoter methylation and gene silencing of CDH13 in pancreatic cancer. Cancer Sci 95:588–591

    Article  PubMed  CAS  Google Scholar 

  22. Hibi K, Kodera Y, Ito K, Akiyama S, Nakao A (2004) Methylation pattern of CDH13 gene in digestive tract cancers. Br J Cancer 91:1139–1142

    PubMed  CAS  Google Scholar 

  23. Widschwendter A, Ivarsson L, Blassnig A, Müller HM, Fiegl H, Wiedemair A, Müller-Holzner E, Goebel G, Marth C, Widschwendter M (2004) CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients. Int J Cancer 109:163–166

    Article  PubMed  CAS  Google Scholar 

  24. Kim WJ, Kim YJ (2009) Epigenetic biomarkers in urothelial bladder cancer. Expert Rev Mol Diagn 9:259–269

    Article  PubMed  CAS  Google Scholar 

  25. Jung S, Jeong D, Kim J, Yi L, Koo K, Lee J, Lee SD, Park JW, Chang B, Kim CH, Kim CJ, Lee MS (2010) The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer. Oncol Rep 23:1675–1682

    Article  PubMed  CAS  Google Scholar 

  26. Huang YW, Jansen RA, Fabbri E, Potter D, Liyanarachchi S, Chan MW, Liu JC, Crijns AP, Brown R, Nephew KP, van der Zee AG, Cohn DE, Yan PS, Huang TH, Lin HJ (2009) Identification of candidate epigenetic biomarkers for ovarian cancer detection. Oncol Rep 22:853–861

    Article  PubMed  CAS  Google Scholar 

  27. Kaufman DS, Shipley WU, Feldman AS (2009) Bladder cancer. Lancet 374:239–249

    Article  PubMed  CAS  Google Scholar 

  28. Lopez-Beltran A (2008) Bladder cancer: clinical and pathological profile. Scand J Urol Nephrol Suppl 218:95–109

    Article  PubMed  Google Scholar 

  29. Yan Q, Zhang ZF, Chen XP, Gutmann DH, Xiong M, Xiao ZY, Huang ZY (2008) Reduced T-cadherin expression and promoter methylation are associated with the development and progression of hepatocellular carcinoma. Int J Oncol 32:1057–1063

    PubMed  CAS  Google Scholar 

  30. Alumkal JJ, Zhang Z, Humphreys EB, Bennett C, Mangold LA, Carducci MA, Partin AW, Garrett-Mayer E, DeMarzo AM, Herman JG (2008) Effect of DNA methylation on identification of aggressive prostate cancer. Urology 72:1234–1239

    Article  PubMed  Google Scholar 

  31. Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glöckner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG (2008) DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 358:1118–1128

    Article  PubMed  CAS  Google Scholar 

  32. Parkin DM (2008) The global burden of urinary bladder cancer. Scand J Urol Nephrol Suppl 218:12–20

    Article  PubMed  Google Scholar 

  33. Rouprêt M, Hupertan V, Yates DR, Comperat E, Catto JW, Meuth M, Lackmichi A, Ricci S, Lacave R, Gattegno B, Richard F, Hamdy FC, Cussenot O (2008) A comparison of the performance of microsatellite and methylation urine analysis for predicting the recurrence of urothelial cell carcinoma, and definition of a set of markers by Bayesian network analysis. BJU Int 101:1448–1453

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are very grateful to editors and reviewers for their valuable comments and to Prof. GW Yang (Professor of English Language, TMU) for his assistance with language editing.

Author information

Authors and Affiliations

  1. Department of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, 300211, Tianjin, China

    Ying-Li Lin, Xiao-Qiang Liu & Chun-Ting Zhang

  2. Tianjin Institute of Urology, 23 Pingjiang Road, 300211, Tianjin, China

    Ying-Li Lin, Xiao-Qiang Liu, Guang Sun & Chun-Ting Zhang

  3. Department of Urology, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, 050051, Shijiazhuang, Hebei, China

    Wen-Ping Li

Authors
  1. Ying-Li Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-Qiang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wen-Ping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chun-Ting Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Guang Sun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, YL., Liu, XQ., Li, WP. et al. Promoter methylation of H-cadherin is a potential biomarker in patients with bladder transitional cell carcinoma. Int Urol Nephrol 44, 111–117 (2012). https://doi.org/10.1007/s11255-011-9961-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-011-9961-6

Keywords

Search

Navigation