Tumorigenic and Prognostic Significance of RASSF1A Expression in Low-grade (WHO Grade 1 and Grade 2) Nonmuscle-invasive Bladder Cancer

Abstract

To investigate RASSF1A expression in an attempt to understand the effect of RASSF1A in low-grade, nonmuscle-invasive bladder cancer (NMIBC). A total of 101 tumor tissues and normal donor-matched adjacent tissues from patients with primary low-grade NMIBC were selected. RASSF1A expression was measured by quantitative real-time polymerase chain reaction and is expressed as the ratio between the normal tissue level and the tumor tissue level (N/T ratio). RASSF1A promoter methylation was assessed using methylation-specific polymerase chain reaction. RASSF1A mRNA expression was significantly lower in patients with RASSF1A methylation than in those with no methylation (P = .046), and RASSF1A mRNA expression was lower in the tumor tissues than in the matched normal bladder mucosa (P < .001). The RASSF1A N/T ratio was greater in grade 2 and large tumors than in grade 1 and small tumors (P < .05 for each). Kaplan-Meier estimates revealed that the differences in the RASSF1A N/T ratio were associated with significant differences in the interval to tumor recurrence (P = .018) in low-grade NMIBC. Multivariate Cox regression analysis showed that the RASSF1A N/T ratio (hazards ratio 2.354, P = .015) was an independent predictor of recurrence. Decreased RASSF1A expression correlates with the transition from normal mucosa to bladder cancer and has prognostic value in low-grade NMIBC.