title: Increased expression of 14-3-3β promotes tumor progression and predicts extrahepatic metastasis and worse survival in hepatocellular carcinoma.
abstract: 14-3-3β is implicated in cell survival, proliferation, migration, and tumor growth; however, its clinical relevance in tumor progression and metastasis have never been elucidated. To evaluate the clinical significance of 14-3-3β, we analyzed the association of 14-3-3β expression and clinicopathologic characteristics in primary and subsequent metastatic tumors of hepatocellular carcinoma patients. 14-3-3β was expressed abundantly in 40 of 55 (70.7%) primary tumors. Increased 14-3-3β expression in primary tumors predicted a higher 5-year cumulative incidence of subsequent extrahepatic metastasis, and multivariate analysis revealed 14-3-3β overexpression was an independent risk factor for extrahepatic metastasis. Patients with increased 14-3-3β expression in primary tumors had worse 5-year overall survival rates, and 14-3-3β overexpression was an independent prognostic factor on Cox regression analysis. Furthermore, stably overexpressed 14-3-3β enhanced hepatocellular carcinoma cell migration and proliferation and increased anchorage-independent cell growth. In addition, in vivo study in a nude-mice model showed tumor formation significantly increased with 14-3-3β overexpression. In conclusion, this is the first report to show that increased 14-3-3β expression is associated with subsequent extrahepatic metastasis and worse survival rates, as well as cancer progression of hepatocellular carcinoma. Thus, 14-3-3β may be a novel prognostic biomarker and therapeutic target in hepatocellular carcinoma.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Tzu-An
authors.initials: TA
authors.lastname: Liu
authors.forename: Yee-Jee
authors.initials: YJ
authors.lastname: Jan
authors.forename: Bor-Sheng
authors.initials: BS
authors.lastname: Ko
authors.forename: Shyh-Chang
authors.initials: SC
authors.lastname: Chen
authors.forename: Shu-Man
authors.initials: SM
authors.lastname: Liang
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Hung
authors.forename: Chiun
authors.initials: C
authors.lastname: Hsu
authors.forename: Tang-Long
authors.initials: TL
authors.lastname: Shen
authors.forename: Yen-Ming
authors.initials: YM
authors.lastname: Lee
authors.forename: Pei-Feng
authors.initials: PF
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.forename: Jun-Yang
authors.initials: JY
authors.lastname: Liou
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; C482982:YWHAB protein, human