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Published in: BMC Urology 1/2016

Open Access 01-12-2016 | Research article

Clinical significance of CDH13 promoter methylation as a biomarker for bladder cancer: a meta-analysis

Authors: Feng Chen, Tao Huang, Yu Ren, Junjun Wei, Zhongguan Lou, Xue Wang, Xiaoxiao Fan, Yirun Chen, Guobin Weng, Xuping Yao

Published in: BMC Urology | Issue 1/2016

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Abstract

Background

Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. However, the clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified.

Methods

A systematic literature search was performed to identify eligible studies in the PubMed, Embase, EBSCO, CKNI and Wanfang databases. The pooled odds ratio (OR) and the corresponding 95 % confidence interval (95 % CI) was calculated and summarized.

Results

Nine eligible studies were included in the present meta-analysis consisting of a total of 1017 bladder cancer patients and 265 non-tumor controls. A significant association was found between CDH13 methylation levels and bladder cancer (OR = 21.71, P < 0.001). The results of subgroup analyses based on sample type suggested that CDH13 methylation was significantly associated with bladder cancer risk in both the tissue and the urine (OR = 53.94, P < 0.001; OR = 7.71, P < 0.001; respectively). A subgroup analysis based on ethnic population showed that the OR value of methylated CDH13 was higher in Asians than in Caucasians (OR = 35.18, P < 0.001; OR = 8.86, P < 0.001; respectively). The relationships between CDH13 methylation and clinicopathological features were also analyzed. A significant association was not observed between CDH13 methylation status and gender (P = 0.053). Our results revealed that CDH13 methylation was significantly associated with high-grade bladder cancer, multiple bladder cancer and muscle invasive bladder cancer (OR = 2.22, P < 0.001; OR = 1.45, P = 0.032; OR = 3.42, P < 0.001; respectively).

Conclusion

Our study indicates that CDH13 methylation may play an important role in the carcinogenesis, development and progression of bladder cancer. In addition, CDH13 methylation has the potential to be a useful biomarker for bladder cancer screening in urine samples and to be a prognostic biomarker in the clinic.
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Literature
2.
go back to reference Fleshner NE, Herr HW, Stewart AK, Murphy GP, Mettlin C, Menck HR. The national cancer data base report on bladder carcinoma. The american college of surgeons commission on cancer and the american cancer society. Cancer. 1996;78:1505–13.CrossRefPubMed Fleshner NE, Herr HW, Stewart AK, Murphy GP, Mettlin C, Menck HR. The national cancer data base report on bladder carcinoma. The american college of surgeons commission on cancer and the american cancer society. Cancer. 1996;78:1505–13.CrossRefPubMed
3.
go back to reference Kantor AF, Hartge P, Hoover RN, Fraumeni Jr JF. Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder. Cancer Res. 1988;48:3853–5.PubMed Kantor AF, Hartge P, Hoover RN, Fraumeni Jr JF. Epidemiological characteristics of squamous cell carcinoma and adenocarcinoma of the bladder. Cancer Res. 1988;48:3853–5.PubMed
4.
go back to reference Gierth M, Burger M. Bladder cancer. Progress in defining progression in nmibc. Nat Rev Urol. 2013;10:684–5.CrossRefPubMed Gierth M, Burger M. Bladder cancer. Progress in defining progression in nmibc. Nat Rev Urol. 2013;10:684–5.CrossRefPubMed
5.
go back to reference Jacobs BL, Lee CT, Montie JE. Bladder cancer in 2010: How far have we come? CA Cancer J Clin. 2010;60:244–72.CrossRefPubMed Jacobs BL, Lee CT, Montie JE. Bladder cancer in 2010: How far have we come? CA Cancer J Clin. 2010;60:244–72.CrossRefPubMed
6.
go back to reference Black PC, Dinney CP. Bladder cancer angiogenesis and metastasis--translation from murine model to clinical trial. Cancer Metastasis Rev. 2007;26:623–34.CrossRefPubMed Black PC, Dinney CP. Bladder cancer angiogenesis and metastasis--translation from murine model to clinical trial. Cancer Metastasis Rev. 2007;26:623–34.CrossRefPubMed
7.
go back to reference Herr HW, Dotan Z, Donat SM, Bajorin DF. Defining optimal therapy for muscle invasive bladder cancer. J Urol. 2007;177:437–43.CrossRefPubMed Herr HW, Dotan Z, Donat SM, Bajorin DF. Defining optimal therapy for muscle invasive bladder cancer. J Urol. 2007;177:437–43.CrossRefPubMed
8.
go back to reference Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, Amiel GE, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: A contemporary series from the bladder cancer research consortium. J Urol. 2006;176:2414–22.CrossRefPubMed Shariat SF, Karakiewicz PI, Palapattu GS, Lotan Y, Rogers CG, Amiel GE, et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: A contemporary series from the bladder cancer research consortium. J Urol. 2006;176:2414–22.CrossRefPubMed
9.
go back to reference Ghavifekr Fakhr M, Farshdousti Hagh M, Shanehbandi D, Baradaran B. DNA methylation pattern as important epigenetic criterion in cancer. Genet Res Int. 2013;2013:317569.PubMedPubMedCentral Ghavifekr Fakhr M, Farshdousti Hagh M, Shanehbandi D, Baradaran B. DNA methylation pattern as important epigenetic criterion in cancer. Genet Res Int. 2013;2013:317569.PubMedPubMedCentral
13.
go back to reference Kim YK, Kim WJ. Epigenetic markers as promising prognosticators for bladder cancer. Int J Urol. 2009;16:17–22.CrossRefPubMed Kim YK, Kim WJ. Epigenetic markers as promising prognosticators for bladder cancer. Int J Urol. 2009;16:17–22.CrossRefPubMed
14.
go back to reference Paluszczak J, Baer-Dubowska W. Epigenetic diagnostics of cancer--the application of DNA methylation markers. J Appl Genet. 2006;47:365–75.CrossRefPubMed Paluszczak J, Baer-Dubowska W. Epigenetic diagnostics of cancer--the application of DNA methylation markers. J Appl Genet. 2006;47:365–75.CrossRefPubMed
15.
go back to reference Takeuchi T, Ohtsuki Y. Recent progress in t-cadherin (cdh13, h-cadherin) research. Histol Histopathol. 2001;16:1287–93.PubMed Takeuchi T, Ohtsuki Y. Recent progress in t-cadherin (cdh13, h-cadherin) research. Histol Histopathol. 2001;16:1287–93.PubMed
16.
go back to reference Andreeva AV, Kutuzov MA. Cadherin 13 in cancer. Genes Chromosomes Cancer. 2010;49:775–90.PubMed Andreeva AV, Kutuzov MA. Cadherin 13 in cancer. Genes Chromosomes Cancer. 2010;49:775–90.PubMed
17.
go back to reference Kuphal S, Martyn AC, Pedley J, Crowther LM, Bonazzi VF, Parsons PG, et al. H-cadherin expression reduces invasion of malignant melanoma. Pigment Cell Melanoma Res. 2009;22:296–306.CrossRefPubMed Kuphal S, Martyn AC, Pedley J, Crowther LM, Bonazzi VF, Parsons PG, et al. H-cadherin expression reduces invasion of malignant melanoma. Pigment Cell Melanoma Res. 2009;22:296–306.CrossRefPubMed
18.
go back to reference Lee SW, Reimer CL, Campbell DB, Cheresh P, Duda RB, Kocher O. H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo. Carcinogenesis. 1998;19:1157–9.CrossRefPubMed Lee SW, Reimer CL, Campbell DB, Cheresh P, Duda RB, Kocher O. H-cadherin expression inhibits in vitro invasiveness and tumor formation in vivo. Carcinogenesis. 1998;19:1157–9.CrossRefPubMed
19.
go back to reference Lee SW. H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nat Med. 1996;2:776–82.CrossRefPubMed Lee SW. H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer. Nat Med. 1996;2:776–82.CrossRefPubMed
20.
go back to reference Zintzaras E, Ioannidis JP. Hegesma: Genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005;21:3672–3.CrossRefPubMed Zintzaras E, Ioannidis JP. Hegesma: Genome search meta-analysis and heterogeneity testing. Bioinformatics. 2005;21:3672–3.CrossRefPubMed
22.
go back to reference DerSimonian R. Meta-analysis in the design and monitoring of clinical trials. Stat Med. 1996;15:1237–48.CrossRefPubMed DerSimonian R. Meta-analysis in the design and monitoring of clinical trials. Stat Med. 1996;15:1237–48.CrossRefPubMed
24.
go back to reference Lin YL, Xie PG, Ma JG. Aberrant methylation of cdh13 is a potential biomarker for predicting the recurrence and progression of non muscle invasive bladder cancer. Med Sci Monit. 2014;20:1572–7.CrossRefPubMedPubMedCentral Lin YL, Xie PG, Ma JG. Aberrant methylation of cdh13 is a potential biomarker for predicting the recurrence and progression of non muscle invasive bladder cancer. Med Sci Monit. 2014;20:1572–7.CrossRefPubMedPubMedCentral
25.
go back to reference Lin YL, Sun G, Liu XQ, Li WP, Ma JG. Clinical significance of cdh13 promoter methylation in serum samples from patients with bladder transitional cell carcinoma. J Int Med Res. 2011;39:179–86.CrossRefPubMed Lin YL, Sun G, Liu XQ, Li WP, Ma JG. Clinical significance of cdh13 promoter methylation in serum samples from patients with bladder transitional cell carcinoma. J Int Med Res. 2011;39:179–86.CrossRefPubMed
26.
go back to reference Lin YL, Liu XQ, Li WP, Sun G, Zhang CT. Promoter methylation of h-cadherin is a potential biomarker in patients with bladder transitional cell carcinoma. Int Urol Nephrol. 2012;44:111–7.CrossRefPubMed Lin YL, Liu XQ, Li WP, Sun G, Zhang CT. Promoter methylation of h-cadherin is a potential biomarker in patients with bladder transitional cell carcinoma. Int Urol Nephrol. 2012;44:111–7.CrossRefPubMed
27.
go back to reference Agundez M, Grau L, Palou J, Algaba F, Villavicencio H, Sanchez-Carbayo M. Evaluation of the methylation status of tumour suppressor genes for predicting bacillus calmette-guerin response in patients with t1g3 high-risk bladder tumours. Eur Urol. 2011;60:131–40.CrossRefPubMed Agundez M, Grau L, Palou J, Algaba F, Villavicencio H, Sanchez-Carbayo M. Evaluation of the methylation status of tumour suppressor genes for predicting bacillus calmette-guerin response in patients with t1g3 high-risk bladder tumours. Eur Urol. 2011;60:131–40.CrossRefPubMed
28.
go back to reference Cabello MJ, Grau L, Franco N, Orenes E, Alvarez M, Blanca A, et al. Multiplexed methylation profiles of tumor suppressor genes in bladder cancer. J Mol Diagn. 2011;13:29–40.CrossRefPubMedPubMedCentral Cabello MJ, Grau L, Franco N, Orenes E, Alvarez M, Blanca A, et al. Multiplexed methylation profiles of tumor suppressor genes in bladder cancer. J Mol Diagn. 2011;13:29–40.CrossRefPubMedPubMedCentral
29.
go back to reference Yu J, Zhu T, Wang Z, Zhang H, Qian Z, Xu H, et al. A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer. Clin Cancer Res. 2007;13:7296–304.CrossRefPubMed Yu J, Zhu T, Wang Z, Zhang H, Qian Z, Xu H, et al. A novel set of DNA methylation markers in urine sediments for sensitive/specific detection of bladder cancer. Clin Cancer Res. 2007;13:7296–304.CrossRefPubMed
30.
go back to reference Maruyama R, Toyooka S, Toyooka KO, Harada K, Virmani AK, Zochbauer-Muller S, et al. Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res. 2001;61:8659–63.PubMed Maruyama R, Toyooka S, Toyooka KO, Harada K, Virmani AK, Zochbauer-Muller S, et al. Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res. 2001;61:8659–63.PubMed
31.
go back to reference Meng J, Yu J, Zhu T, Zhang H, Xu H, Wang W, et al. Detection of bladder cancer by accessing DNA methylation state in urine sediments. Tumor. 2007;27:374–8. Meng J, Yu J, Zhu T, Zhang H, Xu H, Wang W, et al. Detection of bladder cancer by accessing DNA methylation state in urine sediments. Tumor. 2007;27:374–8.
32.
go back to reference Lin Y, Guan T, Xiang D, Sun G, Wu G, Wang H. The clinical significance of the promoter methylation of CDHl3 gene in bladder cancer. Int J Urol Nephrol. 2013;33:174–7. Lin Y, Guan T, Xiang D, Sun G, Wu G, Wang H. The clinical significance of the promoter methylation of CDHl3 gene in bladder cancer. Int J Urol Nephrol. 2013;33:174–7.
33.
go back to reference Kristiansen S, Nielsen D, Soletormos G. Methylated DNA for monitoring tumor growth and regression: How do we get there? Crit Rev Clin Lab Sci. 2014;51:149–59.CrossRefPubMed Kristiansen S, Nielsen D, Soletormos G. Methylated DNA for monitoring tumor growth and regression: How do we get there? Crit Rev Clin Lab Sci. 2014;51:149–59.CrossRefPubMed
34.
go back to reference Qureshi SA, Bashir MU, Yaqinuddin A. Utility of DNA methylation markers for diagnosing cancer. Int J Surg. 2010;8:194–8.CrossRefPubMed Qureshi SA, Bashir MU, Yaqinuddin A. Utility of DNA methylation markers for diagnosing cancer. Int J Surg. 2010;8:194–8.CrossRefPubMed
35.
go back to reference Drilon A, Sugita H, Sima CS, Zauderer M, Rudin CM, Kris MG, et al. A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage i to iiia non-small-cell lung cancers. J Thorac Oncol. 2014;9:1272–7.CrossRefPubMedPubMedCentral Drilon A, Sugita H, Sima CS, Zauderer M, Rudin CM, Kris MG, et al. A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage i to iiia non-small-cell lung cancers. J Thorac Oncol. 2014;9:1272–7.CrossRefPubMedPubMedCentral
36.
go back to reference Moelans CB, de Groot JS, Pan X, van der Wall E, van Diest PJ. Clonal intratumor heterogeneity of promoter hypermethylation in breast cancer by ms-mlpa. Mod Pathol. 2014;27:869–74.CrossRefPubMed Moelans CB, de Groot JS, Pan X, van der Wall E, van Diest PJ. Clonal intratumor heterogeneity of promoter hypermethylation in breast cancer by ms-mlpa. Mod Pathol. 2014;27:869–74.CrossRefPubMed
37.
go back to reference Tahara T, Maegawa S, Chung W, Garriga J, Jelinek J, Estecio MR, et al. Examination of whole blood DNA methylation as a potential risk marker for gastric cancer. Cancer Prev Res (Phila). 2013;6:1093–100.CrossRef Tahara T, Maegawa S, Chung W, Garriga J, Jelinek J, Estecio MR, et al. Examination of whole blood DNA methylation as a potential risk marker for gastric cancer. Cancer Prev Res (Phila). 2013;6:1093–100.CrossRef
38.
go back to reference Konishi K, Watanabe Y, Shen L, Guo Y, Castoro RJ, Kondo K, et al. DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. PLoS One. 2011;6:e27889.CrossRefPubMedPubMedCentral Konishi K, Watanabe Y, Shen L, Guo Y, Castoro RJ, Kondo K, et al. DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. PLoS One. 2011;6:e27889.CrossRefPubMedPubMedCentral
39.
go back to reference Lopez-Beltran A. Bladder cancer: Clinical and pathological profile. Scand J Urol Nephrol Suppl. 2008;42:95-109. Lopez-Beltran A. Bladder cancer: Clinical and pathological profile. Scand J Urol Nephrol Suppl. 2008;42:95-109.
40.
Metadata
Title
Clinical significance of CDH13 promoter methylation as a biomarker for bladder cancer: a meta-analysis
Authors
Feng Chen
Tao Huang
Yu Ren
Junjun Wei
Zhongguan Lou
Xue Wang
Xiaoxiao Fan
Yirun Chen
Guobin Weng
Xuping Yao
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Urology / Issue 1/2016
Electronic ISSN: 1471-2490
DOI
https://doi.org/10.1186/s12894-016-0171-5

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