The clinicopathological significance of BUBR1 overexpression in hepatocellular carcinoma

Background and aims: BUBR1 is a key component of the mitotic spindle checkpoint, and its roles in human cancers are controversial and unclear. The aim of this study was to investigate the clinicopathological significance of BUBR1 expression in hepatocellular carcinoma (HCC). Methods: The BUBR1 protein and its mRNA levels were measured in 58 HCCs, nine high-grade dysplastic nodules and their paired non-tumorous liver tissues by quantitative real-time polymerase chain reaction (qPCR) and western blot, respectively. In addition, immunochemical analysis of the BUBR1 protein was performed in 458 HCCs and 46 dysplastic nodules, and the clinicopathological significance of the BUBR1 expression was evaluated. Results: The BUBR1 expression at both mRNA and protein levels was elevated in two of nine high-grade dysplastic nodules and in 37 of 58 (64%) HCCs. BUBR1 was overexpressed in 207 of 458 (45%) HCCs by immunohistochemistry. Intriguingly, high expression of the BUBR1 was correlated with larger tumour size, higher histological grade, advanced pathological stage, and poor overall and recurrence-free survival. There was a higher frequency of BUBR1 overexpression in cases with positive serum HBsAg than those with negative HBsAg. Moreover, BUBR1 overexpression was associated with P53 staining and high Ki67 labelling indices in HCC tissues. Conclusions: BUBR1 was overexpressed in about 45% HCCs, and its overexpression may be a relative lately event in HCC progression. Overexpression of BUBR1 was associated with worse prognosis and is a potential prognostic factor for patients with HCC.