Proteomics strategies for target identification and biomarker discovery in cancer

Proteomics strategies for target identification and biomarker discovery in cancer
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DOI:
10.2741/3452
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发表时间:
2009-01-01
影响因子:
3.1
通讯作者:
Jimenez, Connie R.
Jimenez, Connie R.
中科院分区:
生物学4区
文献类型:
--
作者:
Rajcevic, Uros;Niclou, Simone P.;Jimenez, Connie R.

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基因组学和蛋白质组学的革命产生了复杂的技术,使人们能够深入了解细胞过程的功能效应器。在肿瘤学中,这些技术导致生物标志物的鉴定,这可能为诊断测试和治疗靶点的开发和鉴定提供起点。为了鉴定和验证蛋白质组中可靠的肿瘤标志物,在串联质谱之前,有必要降低样品的复杂性。这可以通过稳健的分馏和分离技术来完成。本文综述了肿瘤蛋白质组学的发现阶段,即实体瘤和生物体液中靶点识别和生物标志物发现的策略。概述包括不同的蛋白质组学方法,从基于凝胶到基于液相色谱(LC)的蛋白质/肽分离,以及相应的质谱检测。质谱中的定量方法包括基于蛋白质/肽的稳定同位素标记的技术和无标记方法。特别强调的是基于蛋白质组学的生物标志物发现的生物流体(如血浆,尿液,分泌组,脑脊液)和抗血管生成治疗的组织中的目标识别。
The revolution in genomics and proteomics has produced complex technologies enabling an insight into the functional effectors of cellular processes. In oncology these technologies lead to the identification of biological markers which may provide the starting point for the development and identification of diagnostic tests and therapeutic targets. To identify and validate reliable tumor markers within the proteome, it is necessary, prior to tandem mass spectrometry, to reduce sample complexity. This can be done by robust fractionation and separation techniques. This review addresses the discovery stage of onco-proteomics - the strategies for target identification and biomarker discovery in solid tumors and biofluids. The overview includes different proteomic methods, from gel-based to liquid chromatography (LC)-based separations of proteins/peptides, and the corresponding detection by mass spectrometry. The quantitative methods in mass spectrometry include techniques based on stable isotope labeling of proteins/peptides and label-free methods. A particular emphasis is given to proteomics-based biomarker discovery in biofluids (e.g. plasma, urine, secretome, cerebrospinal fluid) and target identification in tissue for anti-angiogenic therapies.