Objective: To investigate the clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer. Methods: Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of PCDH8 in tumour tissue samples obtained from patients with bladder cancer, and in normal bladder epithelial tissue samples obtained from age-and sex-matched control subjects. Methylation status was correlated with demographic, clinical and pathological parameters and disease outcome. Results: PCDH8 promoter methylation was detected in 76/135 (56.3%) patients with bladder cancer and none of 34 (0%) control subjects. Methylation was significantly associated with advanced stage (T 2 -T 4 ), high grade (G 3 ), tumour recurrence, larger tumour diameter (>3 cm) and nonpapillary morphology. In addition, methylation was associated with significantly shorter survival time and was an independent predictor of overall survival. Conclusions: PCDH8 promoter methylation is a common occurrence in bladder cancer, and is associated with malignant behaviour and poor prognosis. Determination of PCDH8 promoter methylation status in tumour tissue may assist in the identification of patients who require aggressive postoperative intervention in order to improve prognosis.

Objective: To investigate the association of downregulated CDH13 expression with invasiveness of bladder transitional cell carcinoma (TCC). Materials and Methods: CDH13 and matrix metalloproteinase-2 (MMP2) expression was detected in 23 normal bladder epithelial tissues and 71 bladder TCC tissues. RNA interference was used to inhibit CDH13 expression in bladder TCC 5637 cells and then analyzed its effects on migration, invasion, adhesion, and proliferation of 5637 cells, as well as MMP2 expression in 5637 cells. Results: The CDH13 expression in bladder TCC tissues was significantly lower than that in normal bladder epithelial tissues. Moreover, the expression of CDH13 from the muscle-invasive group was significantly lower than that from the non-muscle-invasive group. In addition, the MMP2 expression was increased in bladder TCC, especially in muscle-invasive tumors. After the transfection of CDH13 siRNA into 5637 cells, CDH13 expression was significantly decreased, and the migration, invasion, adhesion of 5637 cells, as well as MMP2 expression in 5637 cells was significantly promoted compared with blank and negative controls. Conclusions: Downregulated expression of CDH13 is associated with increased invasion of bladder TCC, and may be due to the enhancement of cell-extracellular matrix adhesion and increased MMP2 expression.

Objective: To investigate the clinical significance of PCDH10 (protocadherin 10) promoter methylation in patients with bladder transitional cell carcinoma (TCC). Materials and Methods: 107 samples of bladder TCC and 38 normal bladder epithelial tissues were investigated using methylation-specific PCR, and the relationships between PCDH10 methylation and clinicopathologic features as well as patients' outcome were analyzed. Results: PCDH10 methylation was detected in 63 (58.9%) bladder TCC samples, but no methylation of PCDH10 was found in controls. Moreover, PCDH10 methylation was significantly associated with larger tumor size (p = 0.0074), non-papillary shape (p = 0.0268), tumor relapse (p = 0.0029), high grade (p = 0.0397), advanced stage (p = 0.0004) and poor prognosis (p = 0.0009). In addition, multivariate analysis indicated that PCDH10 methylation is independently associated with poor outcome and may be used as a useful independent prognostic factor (p = 0.0255). Conclusions: PCDH10 methylation is closely associated with malignancy of bladder TCC and may be used as an independent predictor for patients with bladder TCC.

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