title: Aberrant methylation of CDH11 predicts a poor outcome for patients with bladder cancer.
abstract: DNA methylation is one of the major mechanisms via which tumor suppressor gene inactivation occurs. For example, hypermethylation of the promoter region of cadherin 11 (CDH11), a novel tumor suppressor gene, frequently occurs in human cancer. In the current study, the methylation status of CDH11 was investigated in bladder cancer tissue samples, and the correlation with clinicopathological features and patient outcome was assessed. The methylation status of CDH11 was detected in 146 bladder cancer tissues and 37 normal bladder epithelial tissues using methylation-specific polymerase chain reaction (PCR). In addition, CDH11 mRNA expression levels were examined by quantitative PCR. Subsequently, associations between CDH11 methylation and specific clinicopathological characteristics, as well as patient outcome, were analyzed. Aberrant CDH11 promoter hypermethylation was detected in 63.0% (92/146) of bladder cancer tissues, however, no CDH11 methylation was identified in the control samples; this difference was significant (P<0.05). Furthermore, CDH11 mRNA expression levels were significantly lower in the tumor samples with methylated CDH11 compared with the normal bladder epithelium and tumor samples with unmethylated CDH11 (P<0.05). When the methylation status of CDH11 was correlated with the clinicopathological features, it was identified that CDH11 methylation was significantly associated with poor differentiation (P=0.0440), an advanced disease stage (P=0.0350), a larger tumor size (P=0.0013) and multiple tumors (P=0.0390). In addition, patients with methylated CDH11 exhibited significantly poorer outcomes than patients with unmethylated CDH11 (P=0.0004). Furthermore, multivariate Cox proportional hazard analysis indicated that CDH11 methylation was independently associated with a poor outcome in the patients with bladder cancer, with a relative risk of mortality of 6.852 (P=0.0082; 95% confidence interval, 3.461-16.177). The current findings indicate that aberrant CDH11 methylation frequently occurs in bladder cancer, and correlates with malignant behavior and poor outcome. Thus, CDH11 methylation status may be used as an independent prognostic biomarker for patients with bladder cancer.
authors.affiliation: Department of Urology, Affiliated Xuzhou Hospital of Jiangsu University, Xuzhou Cancer Hospital, Xuzhou, Jiangsu 221000, P.R. China.
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Urology, First Hospital of Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Gui
authors.affiliation: Department of Urology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Ma
keywords: bladder cancer; cadherin 11; methylation