Overexpression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma: Association with tumor progression as determinedby proteomic analysis
Overexpression of alpha enolase in hepatitis C virus-related hepatocellular carcinoma: Association with tumor progression as determinedby proteomic analysis
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DOI：
10.1002/pmic.200401022
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发表时间：
2005-04-01
期刊：
影响因子：
3.4
通讯作者：
Nakamura, K
中科院分区：
文献类型：
--
作者：
Takashima, M;Kuramitsu, Y;Nakamura, K
为了鉴定可作为诊断和治疗丙型肝炎病毒相关肝细胞癌（HCV相关HCC）的分子靶点的蛋白质，我们使用蛋白质组学方法分析人类肝脏样品中的蛋白质表达。采用双向凝胶电泳和液相色谱-串联质谱法分析了26对HCV相关HCC患者的肿瘤和相应的非肿瘤肝脏样本以及6个正常肝脏样本。在肿瘤样品中显示出比非肿瘤样品更强强度的众多斑点之一被鉴定为α烯醇化酶，其是糖酵解途径中的关键酶。这种蛋白的表达随着肿瘤的去分化而增加，并且在低分化HCC中显著高于高分化HCC。免疫印迹分析和免疫组织化学重现了这种模式。α烯醇化酶的表达也与肿瘤大小和静脉浸润呈正相关。这些结果表明，α烯醇化酶是肿瘤进展的生物标志物的候选者之一，值得在HCV相关的HCC中进一步研究。
To identify proteins that could be molecular targets for diagnosis and treatment of hepatitis C virus-related hepatocellular carcinoma (HCV-related HCC), we used a proteomic approach to analyze protein expression in samples of human liver. Twenty-six pairs of tumorous and corresponding nontumorous liver samples from patients with HCV-related HCC and six normal liver samples were analyzed by two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry. One of the numerous spots that showed stronger intensity in tumorous than in nontumorous samples was identified as alpha enolase, a key enzyme in the glycolytic pathway. Expression of this protein increased with tumor dedifferentiation and was significantly higher in poorly differentiated HCC than in well-differentiated HCC. This pattern was reproduced by immunoblot analysis and immunohistochemistry. Expression of alpha enolase also correlated positively with tumor size and venous invasion. These results suggest that alpha enolase is one of the candidates for biomarkers for tumor progression that deserves further investigation in HCV-related HCC.