Molecular Signatures of Non-Small Cell Lung

这个项目的主要目标是发现和验证与以下相关的蛋白质表达模式 临床相关的肿瘤行为。然后，这些标志性蛋白质和表达模式可能会定义早期 检测候选生物标记物，预测肿瘤行为，或识别潜在的新治疗靶点。 与更成熟的基因组学和转录学相比，蛋白质组学有许多理论上的优势 解决这些问题的方法，但受到了一些技术问题的阻碍 标准化，统计分析，并转化到临床，正在被严格识别和 克服困难。范德比尔特肺孢子已经成为肺癌蛋白质组学领域的领先者 通过最初资助期取得的进展，现在，我们正在应用我们拥有的技术 发展到临床肺癌问题，并开发技术更深入地探索人类 蛋白质组。 在这个项目中，我们建议在基于组织和血清的蛋白质组学分析经验的基础上， 在一组高危人群中发现肿瘤进展的新候选生物标志物 肺癌，对治疗的反应和探索新的技术进步来改善我们的蛋白质 发现和识别的努力。我们将确定肿瘤进展的蛋白质组决定因素 侵袭前支气管镜活检患者的呼吸道：一项来自中国的肺癌的嵌套式病例对照研究 与科罗拉多州肺病研究所合作的慢性肺病高危人群的独特队列 孢子。我们将从我们预测的蛋白质组图谱中前瞻性地验证和鉴定血清蛋白质 对EGFrTKIs的反应和对化疗反应的签名(SPECS试验)。重要的是我们 建议开发一种独特的深入分析组织蛋白质组的猎枪分析，结合 基于质谱学的组织和血清中候选生物标志物的定量分析。 这些分子特征将导致对肺肿瘤发生和肿瘤行为的更深入了解 改进的诊断工具，以允许更早和更有针对性的治疗干预，试图减少 肺癌的发病率和死亡率。

The major goals of this project are to discover and validate patterns of protein expression associated with clinically relevant tumor behaviors. These signature proteins and expression patterns may then define early detection biomarker candidates, predictors of tumor behavior, or identify potential new therapeutic targets. Proteomics has many theoretical advantages over the more established genomic and transcriptomic approaches to these questions, but has been hampered by a number of technical problems in standardization, statistical analysis, and translation to the clinic that are being rigorously identified and overcome. The Vanderbilt Lung SPORE has emerged as a leader in the field of lung cancer proteomics through progress made in the initial funding period, and now, we are applying the technology we have developed to clinical lung cancer problems, and developing the technology to probe deeper into the human proteome. In this project, we propose to build on our experience with tissue and serum-based proteomic analysis to discover new candidate biomarkers of tumor progression in a cohort of high risk individuals who develop lung cancer, of response to therapy and to explore new technological advances to improve our protein discovery and identification efforts. We will identify proteomic determinants of tumor progression in the airways of patients with preinvasive bronchial biopsies in a nested case control study of lung cancer from a unique cohort of high-risk individuals with chronic lung disease in collaboration with the Colorado Lung SPORE. We will prospectively validate and identify serum proteins from our proteomic profile predictive of response to EGFrTKIs and develop signatures of response to chemotherapy (SPECS trial). Importantly we propose to develop a unique in depth analysis of the tissue proteome by shotgun analysis, coupled with mass spectrometry-based quantitative analysis of candidate biomarkers in both tissue and serum. These molecular signatures will lead to greater insight into lung tumorigenesis and tumor behavior and improved diagnostic tools to allow earlier and more targeted therapeutic interventions in an attempt to reduce the morbidity and mortality from lung cancer.