Objective  To investigate the expression levels of annexin A2 (ANXA2) and receptor for activated C kinase 1 (RACK1) in hepatocellular carcinoma (HCC) tissues and adjacent normal tissues, to explore the relationships between ANXA2 and RACK1 expression levels and clinicopathological characteristics, and to identify the prognostic value of combined ANXA2 and RACK1 detection in HCC patients.

  Methods  Paraffin-embedded specimens of HCC were collected from 100 patients who underwent radical resection of HCC in The Affiliated Hospital of Nantong University from January 2010 to December 2011. Immunohistochemical staining was used to determine the expression levels of ANXA2 and RACK1. The correlations between ANXA2 and RACK1 levels and survival and recurrence time were analyzed, and the prognostic value of their combined expression levels in HCC was evaluated.

  Results  Immunohistochemical results suggested that the combined expression levels of ANXA2 and RACK1 were related to tumor differentiation, TNM stage and vascular tumor thrombus (P<0.05). Among the 100 tissue samples examined, the expression level of ANXA2 was significantly higher in HCC tissues (42%) than that in adjacent normal tissues (11%, P<0.001), while the expression level of RACK1 was significantly higher in HCC tissues (38%) than that in adjacent normal tissues (18%, P=0.002). The level of ANXA2 expression was correlated with alpha-fetoprotein (AFP) levels (P=0.027), tumor size (P=0.018), the presence of a vascular tumor thrombus (P = 0.035), tumor differentiation (P<0.001), and TNM stage (P<0.001). Sex, age, tumor number, hepatitis B virus (HBV) infection, Child–Pugh score, and the presence of liver cirrhosis (P>0.05) were not correlated with ANXA2 levels. The level of RACK1 expression was correlated with tumor differentiation (P<0.001), the presence of a vascular tumor thrombus (P=0.009), and TNM stage (P<0.001), but not with the other clinical features evaluated (P>0.05). A bivariate Kendall test showed a significant positive correlation between the expression levels of ANXA2 and RACK1 (Z=0.419, P<0.01). The overexpression of ANXA2 or RACK1 indicated a tendency for early relapse. Among 12 patients with early relapse (relapse time <12 months), 11 (91.7%) had high expression levels of both ANXA2 and RACK1. Kaplan–Meier analysis suggested that ANXA2-/RACK1- patients had significantly higher overall survival rates than ANXA2+/RACK1-, ANXA2-/RACK1+, and ANXA2+/RACK1+ patients. Moreover, early relapse was more likely in ANXA2+/RACK1+ patients than ANXA2+/RACK1-, ANXA2-/RACK1+, and ANAX2-/RACK1- patients.

  Conclusions  The combined detection of ANXA2 and RACK1 expression level is an independent predictive factor for survival and recurrence in patients with HCC. Combined analysis of the two proteins is more informative than individual analyses for predicting prognosis.