Low levels of glycoprotein 96 indicate a worse prognosis in early-stage hepatocellular carcinoma patients after hepatectomy

Summary Heat shock proteins are a highly conserved group of cellular proteins and are up-expressed in hepatocellular carcinoma (HCC). As a member of the heat shock protein-90 family, glycoprotein 96 (gp96) modulates immunity and tumorigenicity, is increased during the development of HCC from normal liver tissue, and is considered a pro-oncogenic chaperone. However, the prognostic value of gp96 has not been well clarified. The purpose of this study was to investigate the relationship between gp96 and survival of postoperative HCC patients. The expressions of gp96 protein and messenger RNA were measured by immunohistochemistry and real-time quantitative polymerase chain reaction, respectively. The relations between gp96 expression level and clinicopathological factors were analyzed. Kaplan-Meier survival and Cox regression analyses were used to identify factors associated with prognosis. All normal liver tissue exhibited low gp96 expression, whereas high gp96 expression was present in 54% of HCC tissues. The expression of gp96 protein was inversely correlated with TNM stage ( P  = .037) and tumor recurrence ( P  = .004). Low gp96 expression was an independent risk factor for poor postoperative disease-free survival (hazard ratio, 0.385; 95% confidence interval, 0.226-0.655; P P  = .001). Stratification analysis indicated that high gp96 had better predictive value for tumor recurrence in HCC patients with normal serum α-fetoprotein levels or with TNM stage I and tumor differentiation I-II HCC. In conclusion, gp96 is a potential and reliable prognostic biomarker for tumor recurrence and overall survival in HCC patients after curative resection.