Increased Expression of 14-3-3β Promotes Tumor Progression and Predicts Extrahepatic Metastasis and Worse Survival in Hepatocellular Carcinoma
Increased Expression of 14-3-3β Promotes Tumor Progression and Predicts Extrahepatic Metastasis and Worse Survival in Hepatocellular Carcinoma
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DOI：
10.1016/j.ajpath.2011.08.010
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发表时间：
2011-12-01
影响因子：
6
通讯作者：
Liou, Jun-Yang
中科院分区：
文献类型：
--
作者：
Liu, Tzu-An;Jan, Yee-Jee;Liou, Jun-Yang
14-3-3 β 与细胞存活、增殖、迁移和肿瘤生长有关；然而，其在肿瘤进展和转移中的临床相关性尚未阐明。为了评估 14-3-3 β 的临床意义，我们分析了肝细胞癌患者原发性和后续转移性肿瘤中 14-3-3 β 表达与临床病理特征的关联。 14-3-3 β 在 55 个原发性肿瘤中的 40 个 (70.7%) 中大量表达。原发肿瘤中14-3-3β表达的增加预示着随后肝外转移的5年累积发生率较高，多变量分析显示14-3-3β过度表达是肝外转移的独立危险因素。原发肿瘤中14-3-3β表达增加的患者5年总生存率较差，并且14-3-3β过度表达是Cox回归分析的独立预后因素。此外，稳定过表达的 14-3-3β 增强了肝细胞癌细胞的迁移和增殖，并增加了贴壁依赖性细胞生长。此外，裸鼠模型体内研究表明，随着 14-3-3 β 过度表达，肿瘤形成显着增加。总之，这是第一份表明 14-3-3 β 表达增加与随后的肝外转移和较差的生存率以及肝细胞癌的癌症进展相关的报告。因此，14-3-3β可能是肝细胞癌的新型预后生物标志物和治疗靶点。 (Am J Pathol 2011, 179:2698-2708 DOI: 10.1016/j.ajpath.2011.09.010)
14-3-3 beta 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 14-3-3 beta, we analyzed the association of 14-3-3 beta expression and clinicopathologic characteristics in primary and subsequent metastatic tumors of hepatocellular carcinoma patients. 14-3-3 beta was expressed abundantly in 40 of 55 (70.7%) primary tumors. Increased 14-3-3 beta expression in primary tumors predicted a higher 5-year cumulative incidence of subsequent extrahepatic metastasis, and multivariate analysis revealed 14-3-3 beta overexpression was an independent risk factor for extrahepatic metastasis. Patients with increased 14-3-3 beta expression in primary tumors had worse 5-year overall survival rates, and 14-3-3 beta overexpression was an independent prognostic factor on Cox regression analysis. Furthermore, stably overexpressed 14-3-3 beta 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 14-3-3 beta overexpression. In conclusion, this is the first report to show that increased 14-3-3 beta expression is associated with subsequent extrahepatic metastasis and worse survival rates, as well as cancer progression of hepatocellular carcinoma. Thus, 14-3-3 beta may be a novel prognostic biomarker and therapeutic target in hepatocellular carcinoma. (Am J Pathol 2011, 179:2698-2708 DOI: 10.1016/j.ajpath.2011.09.010)