Background: Bromodomain 4 (BRD4) protein is a double bromodomain-containing protein that binds preferentially to acetylated chromatins. BRD4 is essential for cellular growth and has been implicated in cell cycle control, DNA replication and carcinogenesis. However, its expression profile and prognostic value in urothelial carcinoma of the bladder (UCB) have not been investigated.
Methods: Real-time quantitative PCR (qRT-PCR) and Western blot were used to explore BRD4 expression in UCBs and normal bladder tissues. Moreover immunohistochemistry (ICH) was used to detect the expression of BRD4 in UCBs. Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.
Results: Up-regulated expression of BRD4 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blot when compared with their paired normal bladder tissues. Clinicopathological analysis was showed a significant correlation existed between the higher expression of BRD4 protein with the histological grade, lymph node metastasis and distant metastasis (P < 0.05); Survival analysis by Kaplan-Meier survival curve and log-rank test demonstrated that elevated BRD4 expression in bladder cancer tissue predicted poorer overall survival (OS) compared with group in lower expression. Notably, multivariate analyses by Cox's proportional hazard model revealed that expression of BRD4 was an independent prognostic factor in UCB.
Conclusions: These results suggest that the aberrant expression of BRD4 in human UCB is possibly involved in the tumorigenesis and development, and the BRD4 protein could act as a potential biomarker for prognosis assessment of bladder cancer. Further studies on the cellular functions of BRD4 need to address these issues.
Keywords: Bromodomain 4 protein; Urothelial carcinoma of the bladder; immunohistochemical; prognosis.