Proteomics for hepatocellular carcinoma marker discovery

Proteomics for hepatocellular carcinoma marker discovery
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DOI:
10.1053/j.gastro.2004.09.025
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发表时间:
2004-11-01
期刊:
影响因子:
29.4
通讯作者:
Beretta, L
Beretta, L
中科院分区:
医学1区
文献类型:
--
作者:
Chignard, N;Beretta, L

文献摘要

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血清学标志物的改进和对肝细胞癌(HCC)高危患者的筛查可能会导致更好的HCC检测,早期干预和成功治疗,改善长期结局。蛋白质组学有望发现早期HCC检测和诊断的生物标志物。基于蛋白质组学的分析独特地允许描绘由转录和转录后控制、翻译后修饰和细胞区室之间蛋白质的转变引起的表达模式的全局变化。达到该效果的方法包括直接血清蛋白质谱分析和正常、癌前和早期肿瘤组织中蛋白质表达的比较分析。鉴定引起体液应答的肿瘤抗原组也可能有助于发现用于HCC筛查和诊断的新标志物。如今,二维聚丙烯酰胺凝胶电泳、多维液相色谱、质谱和蛋白质微阵列是可用于生物标志物和药物靶点发现的蛋白质组学工具之一。本文就这些技术及其在肝癌研究中的应用作一综述。我们的目标是提供一个框架,欣赏的承诺,而在同一时间理解背后的挑战,翻译蛋白质组学发现到新的诊断测试。
Refinements of serological markers and screening of patients at high risk for developing hepatocellular carcinoma (HCC) may lead to better HCC detection, earlier intervention, and successful treatment, improving long-term outcomes. Proteomics promises the discovery of biomarkers for early HCC detection and diagnosis. Proteomic-based profiling uniquely allows delineation of global changes in expression patterns resulting from transcriptional and post-transcriptional control, post-translational modifications, and shifts in proteins between cellular compartments. Approaches to that effect include direct serum protein profiling and comparative analysis of protein expression in normal, precancerous, and early-stage tumor tissues. Identification of panels of tumor antigens that elicit a humoral response also may contribute to the discovery of new markers for HCC screening and diagnosis. Today, 2-dimensional polyacrylamide gel electrophoresis, multidimensional liquid chromatography, mass spectrometry, and protein microarrays are among the proteomic tools available for biomarker and drug target discovery. We review these technologies and their application to the study of HCC. Our objective is to provide a framework for appreciating the promise, while at the same time understanding the challenges behind translating proteomics discovery into novel diagnostic tests.