Downregulation of Epstein-Barr virus-induced gene 3 is associated with poor prognosis of hepatocellular carcinoma after curative resection

Epstein-Barr virus-induced gene 3 (EBI3) encodes a secretory glycoprotein, and has previously been identified as upregulated in various types of tumors. The presnet study examined the clinical significance of EBI3 expression for predicting tumor recurrence and survival after resection in hepatocellular carcinoma (HCC). EBI3 expression in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples were detected using western blot analysis. Immunohistochemical staining using tissue microarray with 312 samples from randomly selected patients with HCC who underwent surgery. Survival analysis was performed using univariate and multivariate analyses. EBI3 protein level was higher in L-02 cells and in peri-tumor tissues compared with tumor tissues. Immunohistochemical staining of EBI3 was reduced in HCC tissues in comparison with adjacent normal tissues and significantly associated with tumor invasive characteristics, including tumor thrombus, poor differentiation and large size. Notably, the results suggested that EBI3 was a predictor for tumor recurrence and patient survival, and multivariate analysis indicated EBI3 to be an independent prognostic factor. Even in early-stage disease, low EBI3 expression was also independently associated with increased tumor recurrence and shortened survival. Downregulation of EBI3 in HCC indicated aggressive tumor behaviors and predicted a more severe clinical outcome, which suggests that EBI2 may be a useful biomarker to identify patients at high risk of post-operative recurrence.