Using proteomic approach to identify tumor-associated antigens as markers in hepatocellular carcinoma.

Using proteomic approach to identify tumor-associated antigens as markers in hepatocellular carcinoma.
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DOI:
10.1021/pr800273h
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发表时间:
2008-09
影响因子:
4.4
通讯作者:
Zhang, Jian-Ying
Zhang, Jian-Ying
中科院分区:
生物学2区
文献类型:
--
作者:
Looi, Kok Sun;Nakayasu, Ernesto S.;de Diaz, Raquel A.;Tan, Eng M.;Almeida, Igor C.;Zhang, Jian-Ying

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许多研究表明,细胞内的蛋白质,这是参与癌变,可以激发自身抗体反应。因此,自身抗体可在临床上用于癌症检测和蛋白质组学分析,以鉴定可能参与恶性转化的肿瘤相关抗原(TAA)。肝癌是世界上最常见的肿瘤之一,尤其是肝细胞癌(hepatocellular carcinoma,HCC)。大多数患有HCC的人会在发现后1年内死亡。这种高病死率可部分归因于缺乏能够早期发现的诊断方法。在本研究中,20例HCC患者,30例慢性肝炎(CH),30例肝硬化(LC)患者的血清以及10名正常人的血清中使用的蛋白质组学方法,以确定HCC相关TAAs。从二维凝胶电泳(2DE)中切出34个免疫反应蛋白点,用胰蛋白酶消化,随后通过液相色谱-串联质谱(LC-MS/MS)进行分析。在34个免疫反应蛋白点中,鉴定出28个。其中17例不仅与肝癌血清抗体反应,而且与肝癌前状态下的抗体反应,11例仅与肝癌血清抗体反应,但与肝癌前状态下的抗体不反应。在随后的分析中,选择两种代表性蛋白质HSP 60和HSP 70作为验证目的的示例。免疫测定的结果与蛋白质组学分析的数据一致,支持我们的假设,即用癌前状态中存在的自身抗体鉴定的蛋白质可能不适合用作癌症检测中的TAA标志物。
Many studies have demonstrated that intracellular proteins, which are involved in carcinogenesis, can provoke autoantibody responses. Therefore, autoantibodies can be used clinically for cancer detection and for proteomic analysis in identification of tumor-associated antigens (TAAs) that are potentially involved in malignant transformation. Liver cancer, especially hepatocellular carcinoma (HCC), is one of the most common tumors in the world. The majority of people with HCC will die within 1 year of its detection. This high case fatality rate can partially be attributed to a lack of diagnostic methods that allow early detection. In the present study, sera from 20 patients with HCC, 30 patients with chronic hepatitis (CH), and 30 patients with liver cirrhosis (LC) as well as sera from 10 normal individuals were used in a proteomic approach to identify HCC-related TAAs. Thirty-four immunoreactive protein spots were excised from the two-dimensional gel electrophoresis (2DE), digested with trypsin, and subsequently analyzed by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Of 34 immunoreactive protein spots, 28 were identified. Seventeen of them were not only reactive with serum antibodies in HCC but also with antibodies in pre-HCC conditions, and 11 were only reactive with serum antibodies in HCC but not with antibodies in pre-HCC conditions. In the subsequent analysis, two representative proteins, HSP60 and HSP70, were selected as examples for the validation purpose. The results from immunoassay were consistent with the data from proteomic analysis, supporting our hypothesis that proteins identified with autoantibodies that have been present in precancer conditions may be not appropriate to use as TAA markers in cancer detection.
DOI: 10.1053/j.gastro.2004.09.023
发表时间: 2004-11-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Daniele, B;Bencivenga, A;Tinessa, V
通讯作者: Tinessa, V
DOI: 10.1053/j.gastro.2004.09.025
发表时间: 2004-11-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Chignard, N;Beretta, L
通讯作者: Beretta, L
DOI: 10.1021/pr070525r
发表时间: 2008-02-01
影响因子: 4.4
作者:
Li, Lan;Chen, Sul-hong;Wang, Sheng-qi
通讯作者: Wang, Sheng-qi
DOI: 10.1097/00001574-200405000-00009
发表时间: 2004-05-01
影响因子: 2.5
作者:
Lopez, LJ;Marrero, JA
通讯作者: Marrero, JA
DOI: 10.3748/wjg.v11.i14.2072
发表时间: 2005-04-14
影响因子: 4.3
作者:
Lim, Seung Oe;Park, Sung Gyoo;Park, Cheol Keun
通讯作者: Park, Cheol Keun