High-mobility group box 1 has a prognostic role and contributes to epithelial mesenchymal transition in human hepatocellular carcinoma

Abstract

High-mobility group box 1 (HMGB1), a member of the high-mobility group protein family, was originally characterized as a non-histone, nuclear DNA-binding protein. While the roles of HMGB1 in inflammation and cell differentiation have been previously reported, its role in tumor cell migration and invasion, particularly in hepatocellular carcinoma (HCC), has remained elusive. The present study reported that the expression of HMGB1 in HCC tissues was significantly higher than that in matched tumor-adjacent tissues (P<0.05). HMGB1 was expressed at significantly elevated levels in tumors of patients with large tumor size, high histological grade and advanced tumor-node-metastasis stage (P<0.05). The positive expression of HMGB1 correlated with a poor three-year overall and disease-free survival of HCC patients (P<0.05). In addition, HMGB1 was an independent factor for predicting the three-year overall and disease-free survival of HCC patients (P<0.05). An in vitro experiment revealed that knockdown of HMGB1 inhibited cell migration and invasion in the HCC cell lines Huh7 and MHCC97H (P<0.05). Furthermore, western blot analysis showed that HMGB1 knockdown markedly inhibited epithelial mesenchymal transition in Huh7 and MHCC97H cells. These results suggested that HMGB1 may be utilized as an independent prognostic marker in HCC and may promote tumor progression by promoting cell migration and invasion.