Establishment of prediction system for the prognosis of patients with bladder cancer

点击翻译按钮获取中文摘要

(Purpose) The number of bladder cancer is gradually increasing in Japan. However, the molecular mechanism of bladder cancer progression has not yet fully understood. We attempted to identify genes responsible for tumor progression bladder cancer(Methods and Patients) In this study we enrolled 84 patients who received transurethral resection of bladder tumor (TURBT) and radical cystectomy between 2001 and 2005 in our affiliate hospitals. After obtaining informed consent from all patients, we analyzed the responsible genes for tumor progression in 14 patients with bladder cancer by DNA microarray. For this analysis, we used Ace gene Oligo array (Hitachi Software Engineering Co. Ltd, Yokohama) mounted 30144 genes. We also performed immunohistochemical staining for some candidate genes in tumor tissue specimens. Furthermore, methylation status of promoter region in some candidate genes was examined by methylation specific PCR (MSP)(Results) DNA microarray assay revealed that 21 genes were … More up-regulated and 18 genes were down-regulated in bladder cancer specimens compared with normal bladder tissue. We then confirmed the up-regulation status or down-regulation status of these genes by real-time PCR. Consequently, we picked up 2 genes, S-phase kinase-associated protein 2 (SKP2) and cyclin-dependent kinase subunit 1 (CKS1), as up-regulated genes during the process of bladder cancer progression. The immunohistochemical study demonstrated that expression of SKP2 was similar to that of CKS1 in each tumor specimen, while the expression of p27 was negatively correlated with the expression of these genes. Kaplan-Meier analysis demonstrated that patients with positive expression of either SKP2 or CKS1 had significantly poorer prognosis than the counterparts. MSP analysis revealed that methylation rates of p16INK4a and p14ARF were significantly higher in invasive bladder cancer than those in superficial bladder cancer. Kaplan-Meier analysis demonstrated that patients with p14ARF methylation had significantly poorer prognosis than the counterpart.(Coclusions) Our study suggest that determination of expression levels of SKP2 and CKS1 and methylation status of p16INK4a and p14ARF is useful for prediction of tumor progression and treatment selection in patients with bladder cancer Less