The Expression and Prognosis of FOXO3a and Skp2 in Human Hepatocellular Carcinoma
The Expression and Prognosis of FOXO3a and Skp2 in Human Hepatocellular Carcinoma
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DOI：
10.1007/s12253-009-9171-z
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发表时间：
2009-12-01
影响因子：
2.8
通讯作者：
Shen, Aiguo
中科院分区：
文献类型：
--
作者：
Lu, Mudan;Ma, Jianbo;Shen, Aiguo
叉头盒蛋白（FOXO 蛋白）包含一个功能多样的转录因子大家族，参与细胞增殖、转化、分化和寿命。最近，FOXO3a 的泛素化和蛋白酶体降解已被报道。在这项研究中，我们研究了 FOXO3a 和 Skp2 在人类肝细胞癌进展中的作用。对 91 份标本的福尔马林固定石蜡切片进行免疫组织化学分析。此外，在体外，使用蛋白质印迹分析和蛋白质稳定性研究来研究 FOXO3a 和 Skp2 之间的关系。我们发现FOXO3a的表达与Skp2的表达呈负相关（r = -0.583；p < 0.05），FOXO3a的表达与组织学分级（p = 0.000）、肝硬化（p = 0.015）和肿瘤大小（p = 0.043）显着相关，而Skp2表达与组织学分级（p = 0.000）和肿瘤大小显着相关（ p = 0.005）。 Kaplan-Meier 分析显示，FOXO3a 和 Skp2 低表达者与高表达者的生存曲线在 HCC 中表现出高度显着的分离（p < 0.01）。我们的结果表明 FOXO3a 和 Skp2 可能被认为是人类肝细胞癌的重要预后因素。体外研究表明，FOXO3a 的降解可能依赖于增殖的 Huh7 细胞中 Skp2 的表达。
The forkhead box proteins (FOXO proteins) comprise a large family of functionally diverse transcription factors involved in cellular proliferation, transformation, differentiation and longevity. Recently, ubiquitination and proteasome degradation of FOXO3a have been reported. In this study, we investigated the role of FOXO3a and Skp2 in human hepatocellular carcinoma progression. Immunohistochemical analysis was performed on formalin-fixed paraffin sections of 91 specimens. Furthermore in vitro, western-blot analysis and protein stabilization studies were used to study the relationship between FOXO3a and Skp2. We found that the expression of FOXO3a was negatively related with Skp2 expression (r = -0.583; p < 0.05) and FOXO3a expression correlated significantly with histological grade (p = 0.000), cirrhosis (p = 0.015), and tumor size (p = 0.043) while Skp2 expression correlated significantly with histological grade (p = 0.000) and tumor size ( p = 0.005). Kaplan-Meier analysis revealed that survival curves of low versus high expressers of FOXO3a and Skp2 showed a highly significant separation in HCC (p < 0.01). Our results suggested that FOXO3a and Skp2 may be considered to be important prognosis in human hepatocellular carcinoma. In vitro studies suggested that the degradation of FOXO3a may dependent on the expression of Skp2 in the proliferated Huh7 cells.