Prediction of prognosis and clinical application of gene methylation score in urothelial cancers

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Purpose : Many genes responsible for the bladder cancer progression have been isolated recently. We have reported thathypermethylation of 2 tumor suppressor genes, pl6INK4a and p14ARF is involved in poor prognosis and tumor invasiveness in patients with bladder cancer. In the present study, we examined methylation status of collagen 1A2 gene promoter region in terms of prediction of patient prognosis.Materials and Methods : We examined methylation status of collagen 1A2 gene in the presence and absence of demethylation agent, 5 aza-cytizine in human BOY cultured bladder cancer cells. We examined the frequency of methylation of collagen 1A2 gene in 97 clinical specimens from radical cystectomy and TURBT. Furthermore, we transfected collagen 1A2 gene into human bladder cancer cells and examined cell migration ability and growth rate in both transfectants and control cells.Results : Gene expression of collagen 1A2 gene was increased by 5 aza-cytizine treatment. Collagen 1A2 gene expression in bladder tumors was significantly lower than that in normal bladder tissues. Methylation scores in the bladder tumors are significantly higher that those in normal bladder tissues. Cell migration and growth rate in collagen 1A2 gene transfectants are significantly decreased compared to those in control cells.Conclusions : Collagen 1A2 gene expression is suppressed by the promoter methylation in human bladder cancers. These results suggest that collagen 1A2 gene plays a role in tumor suppressor in human bladder cancer.