SERUM PROTEOMIC BIOMARKERS FOR LUNG CANCER DETECTION AND PROGNOSIS

项目3，目前利用发展研究计划支持发起的一个新的孢子项目 孢子，将利用最先进的Bruker ClinProtTM Ultraflell MALDI TOF/TOF质谱仪 (MS)和Luminex多分析物(LabMAP(R))系统，用于分析来自广泛人群的血清样本 孢子堆积的肺癌患者和对照组。首先，我们将开发一组蛋白质组MS 可在血清中重复检测的特征以及相关的已知血清分析物的优化面板 包括细胞因子、趋化因子、生长/血管生成因子和受体在内的肺癌，以及肺 特定的生物标志物，为肺癌提供强有力的检测和区分。这两者结合在一起 然后，MS/LabMAP(R)血清蛋白质组小组和预测肺癌模型将在 与范德比尔特肺孢子菌合作的独立病例/对照血清系列和一系列 在UPCI孢子PLuSS队列中筛查CT检测到的肺癌。精致的MS/LabMAP(R)面板 预测模型将在一系列预期收集的血清样本中进行测试，这些样本来自 Pluss高危亚队列随后被诊断为新发生的CT检测的肺癌 一次为期5年的积极随访。为了测试这种蛋白质组学方法预测肺癌复发的能力， 在UPCI病例系列之后，未来将有孢子复发、疾病临床核心 进步和生存。基线MALDI-TOF-MS蛋白质组图谱和MS/LabMAP(R)小组将 然后进行评估，并构建一个模型来预测这些临床结果。预测性重现 模型随后将在范德比尔特肺癌孢子病例中进行测试。最后，在实现这些目标的同时， 诊断MS特征(“峰”)将被研究用于肽/蛋白质鉴定，使用一套 肺癌生物标记物发现的生化浓缩/分离和MS分析方法。这个 项目3的翻译目标是开发MS/LabMAP(R)血清图谱和预测算法 对出现临床症状或放射学结果可疑的患者提供更好的诊断 对于肺癌；通过识别MS/LabMAP(R)血清图谱来改进肺癌的早期检测 临床诊断肺部恶性肿瘤前高危受试者CT筛查的应用 MS/LabMAP(R)血清分析用于预测和早期检测肺癌复发。

Project 3, a new SPORE project initiated using Developmental Research Program support in the present SPORE, will utilize the state-of-the-art Bruker ClinProtTM Ultraflexll MALDI TOF/TOF mass spectrometry (MS) and Luminex multianalyte (LabMAP(R)) systems to profile serum samples from an extensive population of SPORE accrued lung cancer patients and controls. First we will develop a panel of proteomic MS features reproducibly detectable in serum together with optimized panels of known serum analytes relevant to lung cancer including cytokines, chemokines, growth/angiogenesis factors and receptors, and lung specific biomarkers, to provide robust detection and discrimination of lung cancer. This combined MS/LabMAP(R) serum proteomic panel and predictive lung cancer model will then be tested in an independent series of case/controls sera in collaboration with the Vanderbilt Lung SPORE and in a series of screening CT-detected lung Cancers in the UPCI SPORE PLuSS cohort. The refined MS/ LabMAP(R) panel and predictive model will be tested in a prospectively collected series of serum samples from subjects in the PLuSS High-Risk Sub-Cohort subsequently diagnosed with a newly-incident CT-detected lung cancer during a 5-year active follow-up. To test the power of this proteomic approach to predict lung cancer recurrence, the UPCI case series will be followed prospectively by the SPORE Clinical Core for recurrence, disease progression, and survival. The baseline MALDI-TOF-MS proteomic profiles and MS/LabMAP(R) panel will then be evaluated and a model constructed to predict these clinical outcomes. The predictive recurrence model will then be tested in the Vanderbilt Lung Cancer SPORE cases. Lastly, in parallel with these aims, diagnostic MS features ("peaks") will be investigated for peptide/protein identification using a suite of biochemical enrichment/fractionation and MS analytical methods for lung cancer biomarker discovery. The translational goals of Project 3 are to develop a MS/LabMAP(R) serum profile and predictive algorithm to provide improved diagnosis of patients presenting with clinical symptoms or radiographic findings suspicious for lung cancer; to improve early detection of lung cancer by identifying a MS/LabMAP(R) serum profile in high-risk subjects prior to the clinical diagnosis of a lung malignancy by screening CT; and the application of MS/LabMAP(R) serum profiling for prediction and early detection of lung cancer recurrence.