Overexpression of 14-3-3ε predicts tumour metastasis and poor survival in hepatocellular carcinoma

Aims: The results of our earlier studies suggested that 14-3-3 epsilon is involved in cancer cell survival and growth. However, it is not clear whether 14-3-3 epsilon plays a role in tumour metastasis and patient outcome. The aim of this study was to determine whether 14-3-3 epsilon is a marker for predicting hepatocellular carcinoma (HCC) metastasis and survival. Methods and results: One hundred and fourteen patients with tissue-diagnosed primary HCC were followed for an average of 58.6 months. 14-3-3 epsilon in liver tissues was analysed by immunohistochemistry, and quantified by a Quick score system. Correlation of 14-3-3 epsilon with patient survival and metastasis was analysed with a Wilcoxon signed rank test, Kaplan-Meier survival curves, and Cox proportional hazard regression. Seventy-one of 114 patients (62.3%) had a significant increase of 14-3-3 epsilon expression in HCC tissues, whereas normal tissues expressed weak or undetectable 14-3-3 epsilon. Elevated 14-3-3 epsilon expression was significantly associated with shortened overall survival and progression-free survival. Furthermore, 14-3-3 epsilon overexpression increased the risk of metastasis 4.6-fold. Conclusions: Overexpression of 14-3-3 epsilon in primary HCC tissues predicts a high risk of extrahepatic metastasis and worse survival, and is a potential therapeutic target.