López Elena, Cho William C S
Hospital Universitario Niño Jesús, Department of Oncohematology of Children, Madrid 28009, Spain.
Int J Mol Sci. 2012 Sep 26;13(10):12287-314. doi: 10.3390/ijms131012287.
Massive evidence suggests that genetic abnormalities contribute to the development of lung cancer. These molecular abnormalities may serve as diagnostic, prognostic and predictive biomarkers for this deadly disease. It is imperative to search these biomarkers in different tumorigenesis pathways so as to provide the most appropriate therapy for each individual patient with lung malignancy. Phosphoproteomics is a promising technology for the identification of biomarkers and novel therapeutic targets for cancer. Thousands of proteins interact via physical and chemical association. Moreover, some proteins can covalently modify other proteins post-translationally. These post-translational modifications ultimately give rise to the emergent functions of cells in sequence, space and time. Phosphoproteomics clinical researches imply the comprehensive analysis of the proteins that are expressed in cells or tissues and can be employed at different stages. In addition, understanding the functions of phosphorylated proteins requires the study of proteomes as linked systems rather than collections of individual protein molecules. In fact, proteomics approaches coupled with affinity chromatography strategies followed by mass spectrometry have been used to elucidate relevant biological questions. This article will discuss the relevant clues of post-translational modifications, phosphorylated proteins, and useful proteomics approaches to identify molecular cancer signatures. The recent progress in phosphoproteomics research in lung cancer will be also discussed.
大量证据表明,基因异常与肺癌的发生发展有关。这些分子异常可作为这种致命疾病的诊断、预后和预测生物标志物。在不同的肿瘤发生途径中寻找这些生物标志物至关重要,以便为每一位肺癌患者提供最恰当的治疗。磷酸化蛋白质组学是一种很有前景的技术,可用于识别癌症的生物标志物和新型治疗靶点。数以千计的蛋白质通过物理和化学结合相互作用。此外,一些蛋白质可以在翻译后对其他蛋白质进行共价修饰。这些翻译后修饰最终依次在序列、空间和时间上产生细胞的新兴功能。磷酸化蛋白质组学临床研究意味着对细胞或组织中表达的、可在不同阶段应用的蛋白质进行全面分析。此外,了解磷酸化蛋白质的功能需要将蛋白质组作为相互关联的系统进行研究,而不是将其作为单个蛋白质分子的集合。事实上,蛋白质组学方法与亲和色谱策略相结合,再结合质谱分析,已被用于阐明相关生物学问题。本文将讨论翻译后修饰、磷酸化蛋白质的相关线索,以及用于识别分子癌症特征的有用蛋白质组学方法。还将讨论肺癌磷酸化蛋白质组学研究的最新进展。