Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus

Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus
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DOI:
10.1002/pmic.200300712
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发表时间:
2004-07-01
期刊:
影响因子:
3.4
通讯作者:
Okita, K
Okita, K
中科院分区:
生物学3区
文献类型:
--
作者:
Yokoyama, Y;Kuramitsu, Y;Okita, K

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肝细胞癌(HCC)是日本的主要死亡原因。丙型肝炎病毒(HepatitisCvirus,HCV)在肝癌患者中的发病率较高,已被认为在肝癌的发生发展中起重要作用。为了解HCV感染后肝癌发生的机制,我们采用双向电泳技术对HCV感染患者的肿瘤组织和非肿瘤组织的蛋白质谱进行了比较研究。超过50%的患者的HCC组织中有11个斑点减少。使用肽质量指纹图谱与基质辅助激光解吸/电离-飞行时间质谱法鉴定了11个斑点中的8个蛋白质。这些蛋白质是肝型醛缩酶、原肌球蛋白β-链、己酮糖激酶、烯酰辅酶A水合酶、白蛋白、smoothelin、铁蛋白轻链和辅酶I。烯酰辅酶A水合酶、原肌球蛋白β链、酮己糖激酶、肝型醛缩酶和β-内酰胺酶1的强度显著不同(p < 0.05)。其中8种蛋白表达的降低是HCC的特征性变化。我们将讨论这些蛋白质对肝细胞功能丧失的影响以及HCV相关HCC致癌的可能性。
Hepatocellular carcinoma (HCC) is a major cause of death in Japan. It has been suggested that hepatitis C virus (HCV) plays an important role in hepatocarcinogenesis, because of high incidence among the patients. To understand the mechanism of hepatocarcinogenesis after HCV infection, we performed a comparative study on the protein profiles between tumorous and nontumorous specimens from the patients infected with HCV by means of two-dimensional electrophoresis. Eleven spots were decreased in HCC tissues from over 50% of the patients. Eight proteins out of 11 spots were identified using peptide mass fingerprinting with matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. These proteins were liver type aldolase, tropomyosin beta-chain, ketohexokinase, enoyl-CoA hydratase, albumin, smoothelin, ferritin light chain, and arginase 1. The intensity of enoyl-CoA hydratase, tropomyosin beta-chain, ketohexokinase, liver type aldolase, and arginase 1 was significantly different (p < 0.05). The decrease of 8 proteins was characteristic in HCC. We will discuss the implication of these proteins for the loss of function of hepatocytes and for the possibility of carcinogenesis of HCV-related HCC.