Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Mol Cell Proteomics. 2012 Oct;11(10):916-32. doi: 10.1074/mcp.M111.015370. Epub 2012 Jul 3.
Advances in proteomic analysis of human samples are driving critical aspects of biomarker discovery and the identification of molecular pathways involved in disease etiology. Toward that end, in this report we are the first to use a standardized shotgun proteomic analysis method for in-depth tissue protein profiling of the two major subtypes of nonsmall cell lung cancer and normal lung tissues. We identified 3621 proteins from the analysis of pooled human samples of squamous cell carcinoma, adenocarcinoma, and control specimens. In addition to proteins previously shown to be implicated in lung cancer, we have identified new pathways and multiple new differentially expressed proteins of potential interest as therapeutic targets or diagnostic biomarkers, including some that were not identified by transcriptome profiling. Up-regulation of these proteins was confirmed by multiple reaction monitoring mass spectrometry. A subset of these proteins was found to be detectable and differentially present in the peripheral blood of cases and matched controls. Label-free shotgun proteomic analysis allows definition of lung tumor proteomes, identification of biomarker candidates, and potential targets for therapy.
蛋白质组学分析技术在人类样本中的进展正在推动生物标志物发现和疾病病因相关分子途径鉴定的关键方面。为此，在本报告中，我们首次使用标准化的鸟枪法蛋白质组学分析方法对非小细胞肺癌的两个主要亚型和正常肺组织进行深入的组织蛋白分析。我们从鳞状细胞癌、腺癌和对照标本的混合人样本分析中鉴定出 3621 种蛋白质。除了先前被认为与肺癌有关的蛋白质外，我们还鉴定出了新的途径和多个具有潜在治疗靶点或诊断生物标志物意义的差异表达蛋白，包括一些未通过转录组谱分析鉴定的蛋白。这些蛋白质的上调通过多重反应监测质谱法得到了确认。其中一部分蛋白质被发现可以在病例和匹配对照的外周血中检测到并存在差异。无标记的鸟枪法蛋白质组学分析可定义肺癌肿瘤蛋白质组、鉴定生物标志物候选物和治疗的潜在靶点。
