Involvement of 14-3-3γ overexpression in extrahepatic metastasis of hepatocellular carcinoma.
The 14-3-3γ 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 14-3-3γ 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 14-3-3γ in these primary and metastatic samples was measured with semiquantitative immunohistochemistry analysis. Overexpression of 14-3-3γ was observed in 38 (69.1%) of the primary tumors, correlated significantly with a high α-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%, 14-3-3γ positive versus negative; P = .012). Furthermore, 14-3-3γ 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% ± 10.6% versus 48.6% ± 8.2%, respectively). Elevated expression of 14-3-3γ 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.
Ko
Bor-Sheng
BS
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
Lai
I-Rue
IR
Chang
Tzu-Ching
TC
Liu
Tzu-An
TA
Chen
Shyh-Chang
SC
Wang
John
J
Jan
Yee-Jee
YJ
Liou
Jun-Yang
JY
D048948:14-3-3 Proteins / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology / Q000556:secondary; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000503:physiopathology; D011379:Prognosis; D015996:Survival Rate
D048948:14-3-3 Proteins