The Causal Relationship between RUNX3 and Bladder Tumor / 대한비뇨기과학회지

ABSTRACT

PURPOSE: We investigated the methylation pattern of RUNX3 to determine whether aberrant methylation events are risk factors for bladder tumor development, recurrence, and progression. MATERIALS AND METHODS: A hospital based, case-control investigation was carried out in 124 bladder tumor specimens and 20 normal bladder mucosae. The methylation pattern of RUNX3 was determined using MS- PCR and direct DNA sequencing. RUNX3 mRNA expression levels were assessed by RT-PCR. RESULTS: All normal bladder mucosae were unmethylated. On the other hand, bladder tumor tissues showed either unmethylated, methylated, or both unmethylated and methylated patterns. Methylation of RUNX3 promoter region was significant as a risk factor for bladder tumor development (p<0.01, OR=107.55, 95% CI=6.33-1827.39). The methylation type was more frequent in invasive tumors, compared with superficial bladder tumors (p=0.01, OR=2.95, 95% CI=1.16-7.47). Both recurrence (p=0.02, OR= 3.70, 95% CI=1.19-11.46) and subsequent tumor progression were significantly associated with the methylation of the RUNX3 promoter region (p=0.01, OR=5.63, 95% CI=1.23-25.82). The mutations in 3 cases out of 23 bladder tumor tissues were observed in contrast with normal bladder mucosae. CONCLUSIONS: These results suggest not only the possibility that RUNX3 is a tumor suppressor gene responsible for bladder tumor, but also that it may be a useful prognostic marker for bladder tumor recurrence and progression.