Abstract
BackgroundMethylation 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.MethodsA 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.ResultsNine 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).ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12894-016-0171-5) contains supplementary material, which is available to authorized users.
Highlights
Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers
Inclusion criteria The eligible studies met the following criteria: 1) the patients were diagnosed with bladder cancer based on histopathology; 2) CDH13 methylation was evaluated in different types of samples, such as tissue, serum, plasma and urine; 3) regarding control samples by cystoscopy and histopathological confirmation, tissue samples belonged to normal tissues, while fluid samples such as serum, plasma or urine were from healthy individuals or patients with benign urological diseases; 4) the studies showed the associations between CDH13 methylation and clinicopathological parameters, including gender, cancer tumor/node/metastasis (TNM)
8 studies assessed the association between CDH13 methylation and bladder cancer risk, 5 studies evaluated the relationship between CDH13 methylation and gender, 5 studies explored the association between CDH13 methylation and tumor number, 4 studies reported the tumor grade, and 5 studies evaluated the effect of clinical stage (T2-T4 vs Ta-T1)
Summary
Methylation of the tumor suppressor gene H-cadherin (CDH13) has been reported in many cancers. The clinical effect of the CDH13 methylation status of patients with bladder cancer remains to be clarified. DNA methylation is the most common epigenetic alteration in human cancers [9,10,11]. The detection of aberrantly methylated genes can be used as a diagnostic or prognostic biomarker for human cancers, especially when the aberrant methylation silences tumor suppressor genes [12,13,14]. CDH13, a tumor suppressor gene (TSG), is called H-cadherin or T-cadherin and plays a pivotal role in cell–cell adhesion [16]. CDH13 promoter methylation has been reported in some human cancers including bladder cancer [16]
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