MOLECULAR SIGNATURES OF NSCLC

非小细胞肺癌的分子特征

• 批准号: 8136270
• 负责人: PIERRE P. MASSION
• 金额: $ 37.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8136270
• 关键词: African American; Behavior; Biological Assay; Biological Markers; Biopsy; Blood; Cell Line; Chronic lung disease; Clinic; Clinical; Cohort Studies; Collaborations; Colorado; Communities; Complement; Complex Mixtures; Coupled; Data; Data Set; Development; Diagnostic; Dimensions; Disease; Doctor of Philosophy; Early Diagnosis; Eastern Cooperative Oncology Group; Fine needle aspiration biopsy; Funding; Genomics; Goals; Human; Individual; Lead; Lesion; Literature; Lung; Lung Adenocarcinoma; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Mass Spectrum Analysis; Measures; Methods; Modification; Molecular Profiling; Molecular Weight; Morbidity - disease rate; Nested Case-Control Study; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Patients; Pattern; Peptides; Phenotype; Phosphorylation; Population; Proteins; Proteome; Proteomics; Randomized Clinical Trials; Reproducibility; Reproduction spores; Sampling; Serum; Serum Proteins; Shotguns; Signal Transduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Standardization; Techniques; Technology; Testing; Texas; Therapeutic Intervention; Tissues; Translations; Universities; airway epithelium; base; cancer proteomics; candidate marker; chemotherapy; clinical application; clinically relevant; cohort; computerized data processing; experience; follow-up; high risk; improved; insight; lung tumorigenesis; mortality; neoplastic cell; new therapeutic target; novel strategies; numb protein; pre-clinical; programs; prospective; protein expression; response; stable isotope; tool; transcriptomics; tumor; tumor progression

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.

该项目的主要目标是发现和验证与 临床相关的肿瘤行为。这些标志性蛋白质和表达模式可能会尽早定义 检测生物标志物候选物，肿瘤行为的预测因子或识别潜在的新治疗靶标。 蛋白质组学比更具成熟的基因组和转录组具有许多理论上的优势 解决这些问题的方法，但受到许多技术问题的阻碍 标准化，统计分析和转化为严格识别的诊所 克服。范德比尔特肺孢子已成为肺癌蛋白质组学领域的领导者 通过最初的资金时期取得的进展，现在，我们正在应用我们拥有的技术 发展为临床肺癌问题，并开发了该技术以更深入地探究人类 蛋白质组。 在这个项目中，我们建议以组织和基于血清的蛋白质组学分析的经验为基础 发现在发展的高风险人群中肿瘤进展的新候选生物标志物 肺癌，对治疗的反应并探索改善蛋白质的新技术进步 发现和识别工作。我们将确定肿瘤进展的蛋白质组学决定因素 在肺癌的嵌套病例对照研究中，来自A 与科罗拉多肺合作的高风险患者的独特同类 孢子。我们将从我们的蛋白质组学曲线中验证和鉴定血清蛋白的预测 对EGFRTKIS的反应并发展对化学疗法的反应（规格试验）。重要的是我们 建议通过shot弹枪分析对组织蛋白质组进行独特的深度分析，并与 基于质谱的定量分析组织和血清中的候选生物标志物。 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，以及 改进的诊断工具可以允许早期和更具针对性的治疗干预措施来减少 肺癌的发病率和死亡率。