Defective Beclin-1 and elevated hypoxia-inducible factor (HIF)-1α expression are closely linked to tumorigenesis, differentiation, and progression of hepatocellular carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. Autophagy and hypoxia have been involved in HCC tumorigenesis. In the present study, we examined the relationship between Beclin-1 expression and hypoxia-inducible factor (HIF)-1α expression in HCC by immunohistochemistry on 65 tumor specimens. Their correlations with clinicopathological features were also explored. There was a loss of Beclin-1 protein expression in 49.2 % of HCC. Beclin-1 expression was only significantly correlated with virus infection status (p = 0.025) and marginally associated with HCC grade (p = 0.057). Forty-two tumors (64.6 %) showed high HIF-1α expression, and it was significantly associated with large tumor size (p = 0.003), multifocal tumors (p = 0.038), and advanced stage (p = 0.043). Beclin-1 expression was significantly associated with HIF-1α expression (p = 0.001). HCC cases were further stratified according to their hypoxia status into hypoxic and normoxic groups. In the hypoxic group, Beclin-1 expression was negatively correlated with HCC high tumor grade (p < 0.001), advanced stage (p = 0.013), large size (p = 0.002), and multifocal tumors (p = 0.047). In the normoxic group, no significant relations between Beclin-1 expression and any of the clinicopathological parameters were identified. Our findings that reduced Beclin-1 and high HIF-1α expression are associated with the development and progression of HCC may provide molecular therapeutic targets toward inhibiting HCC development and progression.