The 14-3-3 gamma protein is an important regulator of various cellular and physiologic functions Overexpression promotes cell proliferation and induces cancer cell polyploidization Production is up regulated in human hepatocellular carcinoma However, the clinical significance of 14 3 3 gamma for human hepatocellular carcinoma metastasis and survival has not been clarified In this study, 55 patients with human hepatocellular carcinoma were enrolled, and 18 of them were identified as having extrahepatic metastases Expression of 14 3-3 gamma in these primary and metastatic samples was measured with semiquantitative immunohistochemistry analysis Overexpression of 14 3-3 gamma was observed in 38 (69 1%) of the primary tumors correlated significantly with a high alpha-fetoprotein concentration (P = 003), and predicted a higher probability of extrahepatic metastasis (cumulative probabilities at 5 years 42 2% +/- 8 0% versus 5 9% +/- 5 7%, 14-3-3 gamma positive versus negative, P = 012) Furthermore, 14-3 3 gamma overexpression was associated with a worse 5-year overall survival rate (81 6% +/- 9 6% versus 59 5% +/- 8 1%, respectively) and a worse 5-year progression-free survival rate (75 6% +/- 106% versus 48 6% +/- 8 2% respectively) Elevated expression of 14 3-3 gamma in human hepatocellular carcinoma predicts extrahepatic metastasis and worse survival The protein thus is a candidate biomarker and a potential target for novel therapies against human hepatocellular carcinoma progression and metastasis
