Identification by Differential Tissue Proteome Analysis of Talin-1 as a Novel Molecular Marker of Progression of Hepatocellular Carcinoma
Identification by Differential Tissue Proteome Analysis of Talin-1 as a Novel Molecular Marker of Progression of Hepatocellular Carcinoma
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DOI：
10.1159/000330734
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发表时间：
2011-01-01
期刊：
影响因子：
3.5
通讯作者：
Sakamoto, Michiie
中科院分区：
文献类型：
--
作者：
Kanamori, Hideaki;Kawakami, Takao;Sakamoto, Michiie
目的：肝细胞癌是一种多阶段的肿瘤进展过程。这项研究探讨了其分子特征，以确定与肝细胞癌进展相关的新的候选蛋白。方法：采用液-质联用技术，对2例肝移植术后4例早期肝细胞癌和4例非肝细胞癌组织的蛋白质组进行比较。对106个肝细胞癌结节进行免疫组织化学染色，以验证蛋白质组学分析结果。结果：统计分析筛选出区分肝细胞癌与非肝细胞癌的多肽峰。对这些多肽峰的串联质谱学数据进行数据库搜索，发现了61种蛋白质，其中包括细胞骨架蛋白talin-1，它在肝细胞癌中上调。肝细胞癌结节中Talin-1的表达水平与肝细胞癌的去分化程度显著相关(p=0.001)。随访的临床病例显示Talin-1表达上调与术后复发时间缩短相关(p=0.039)，这可能与talin-1上调的肝细胞癌门静脉侵袭率较高(p=0.029)有关。结论：蛋白质组学分析表明Talin-1是一种有希望的肝细胞癌标志物。Talin-1的上调与肝细胞癌的进展有关，可作为预后的标志物。版权所有(C)2011 S.Karger AG，巴塞尔
Objective: Hepatocellular carcinoma (HCC) is characterized by a multistage process of tumor progression. This study addressed its molecular features to identify novel protein candidates involved in HCC progression. Methods: Using liquid chromatography-tandem mass spectrometry, proteomes of 4 early HCCs and 4 non-HCC tissues derived from 2 cases of liver transplant surgery were compared with respect to the separation profiles of their tryptic peptides. Immunohistochemistry was performed on 106 HCC nodules to confirm the results of the proteomic analysis. Results: Statistical analysis of the profiles selected the peptide peaks differentiating HCC from non-HCC. A database search of the tandem mass spectrometry data from those peptide peaks identified 61 proteins, including a cytoskeletal protein, talin-1, as upregulated in HCC. Talin-1 expression levels in HCC nodules were significantly associated with the dedifferentiation of HCC (p = 0.001). A follow-up survey of the examined clinical cases revealed a correlation between talin-1 upregulation and a shorter time to recurrence after resection (p = 0.039), which may be related to the higher rate of portal vein invasion in HCCs with talin-1 up-regulation (p = 0.029). Conclusions: Proteomic analysis led to identification of talin-1 as a promising HCC marker. Talin-1 upregulation is associated with HCC progression and may serve as a prognostic marker. Copyright (C) 2011 S. Karger AG, Basel