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Use of Proteomics Analysis for Molecular Precision Approaches in Cancer Therapy

机译：蛋白质组学分析在癌症治疗中分子精确方法的应用

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The rapidly expanding data sets derived from genomic and transcriptomic analyses have allowed greater understanding of structural and functional network patterns within the genome resulting in a realignment of thinking within a systems biologic framework of cancer. However, insofar as spatially and temporally dynamic differential gene expression at the protein level is the mediate effector of cellular behavior and, in view of extensive post translational modi?cation (PTM), the need for sensitive, quantitative, and high throughput proteomic analytic techniques has emerged. To circumvent the problems of tissue sample heterogeneity, laser capture microdissection (LCM) allows for the acquisition of homogeneous cell populations. Using different ? uorescent dyes to label protein samples prior to gel electrophoresis, 2-D DIGE (two- dimensional differential in-gel electrophoresis) can, with reasonable sensitivity, process three protein samples on the same gel allowing for intragel relative quanti?cation. MudPIT (multidimensional protein identi?cation technology) is a non-gel approach exploiting the unique physical properties of charge and hydrophobicity which allows the separation of peptide mixtures as well as direct MS (mass spectrometry) and database searching. The introduction of iTRAQ (isobaric tags for relative and absolute quanti?cation) achieves labeling of all peptides by employing an 8-plex set of amine reactive tags to derivatize peptides at the N-terminus and lysine side chains allowing for absolute quanti?cation and assessment of PTM. These and other new laboratory technologies, along with improved bioinformatics tools, have started to make signi? cant contributions in cancer diagnostics and treatments.
机译：从基因组和转录组学分析获得的迅速扩展的数据集已使人们对基因组内的结构和功能网络模式有了更深入的了解，从而导致了癌症系统生物学框架内思维的重新排列。然而，就蛋白质水平的时空动态差异基因表达而言，是细胞行为的中介因子，鉴于广泛的翻译后修饰（PTM），需要灵敏，定量和高通量的蛋白质组学分析技术已经出现。为了避免组织样品异质性的问题，激光捕获显微切割（LCM）允许采集均质的细胞群。使用不同？荧光染料在凝胶电泳之前标记蛋白质样品，二维DIGE（二维差分凝胶电泳）可以以合理的灵敏度在同一凝胶上处理三个蛋白质样品，以进行凝胶内相对定量。 MudPIT（多维蛋白质鉴定技术）是一种非凝胶方法，利用电荷和疏水性的独特物理特性，可分离肽混合物以及直接进行MS（质谱）和数据库搜索。 iTRAQ（用于相对和绝对定量的等压标记）的引入通过使用8组胺反应性标记在N端和赖氨酸侧链上衍生化肽实现了所有肽的标记，从而实现了绝对定量和绝对定量。 PTM评估。这些以及其他新的实验室技术，以及经过改进的生物信息学工具，已开始引起人们的关注。不能在癌症诊断和治疗中做出贡献。

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