Aberrant methylation of CDH11 predicts a poor outcome for patients with bladder cancer

Abstract

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.

Clinical and prognostic association of oncogene cadherin 11 in gastric cancer

“…Multivariate analysis that the CDH11 promoter is hypermethylated in bladder cancer, melanoma and head and necktumors (31). The present study analyzed the methylation status of CDH11 in GC and normal gastric tissues.…”

Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration

“…22e27 In particular, Cad-11 plays a role in epithelial-to-mesenchymal transition, which represents an inflammation-induced response that has a fundamental role in the progression from chronic inflammation to cancer. 28,29 Dysregulation of Cad-11 expression has been associated with many pathologic processes such as inflammation (eg, rheumatoid arthritis 18 ), fibrosis (eg, kidney, 30 pulmonary, 31 dermal 20 ), and cancer (eg, prostatic, 32 breast, 33 gastric, 34 bladder, 35 renal carcinoma, 34 and glioblastoma 36 ). Specifically, Cad-11 is a mesenchymal cadherin that is associated with more undifferentiated and aggressive cancer.…”

The prognostic role of epigenetic dysregulation in bladder cancer: A systematic review

“…Finally, all of the Portuguese studies were conducted by Dr. Carmen Jerónimo's group in IPO (Portuguese Oncology Institute) [32][33][34][35][36]. Regarding Asian studies, significant contributions have been made by Dr. Ying-Li Lin [37][38][39][40][41][42][43] at Jiangsu University and Dr. Liqun Zhou (especially in UTUC studies) [44][45][46]…”

“…The studies by Dr. Lin at JU have reported that methylation of CDH13 is associated with increased recurrence risk (p=0.0043), shorter time to progression (p=0.006), lower RFS (p<0.0001) [43] and with an increased risk of death (p=0.0071) [41]. In another of his studies, CDH11 methylation correlated with poor OS (p=0.0004) [40]. However, CDH13 methylation had no prognostic value in other cohorts [13,66].…”