Overexpression of high-mobility group box 1 correlates with tumor progression and poor prognosis in human colorectal carcinoma

Abstract

High-mobility group box 1 (HMGB1) has been implicated in a variety of biologically important processes, including transcription, DNA repair, V(D)J recombination, differentiation, development, and extracellular signaling. The increased expression of HMGB1 has been described in colorectal cancer (CRC). However, there is no report about the correlation of HMGB1 with clinicopathologic features, including the survival of patients with CRC. In present study, we investigated HMGB1 expression and its prognostic significance in CRC by performing immunohistochemical analysis, using a total of 192 paraffin-embedded archival CRC samples. Moreover, disruption of endogenous HMGB1 protein through a siRNA knockdown technique was performed to investigate the possible role of HMGB1 in the process of tumor invasion and metastasis. Overexpression of HMGB1 was shown in 55.7% cases. Statistical analysis showed that HMGB1 expression was positively correlated with tumor invasion (P = 0.048), lymph node metastasis (P = 0.011), distant metastasis (P = 0.031), and Duke's stage (P = 0.029) of CRC patients. Patients with higher HMGB1 expression had shorter overall survival time, whereas patients with lower level of HMGB1 had better survival. Multivariate analysis suggested that HMGB1 expression might be an independent prognostic indicator for the survival of patients with CRC. Disruption of endogenous HMGB1 protein through a siRNA knockdown technique was shown to suppress substantially the invasion ability of SW620 cells. Our results suggest that HMGB1 protein is a valuable marker for progression of CRC patients. High HMGB1 expression is associated with poor overall survival in patients with CRC.