SERUM PROTEOMIC BIOMARKERS FOR LUNG CANCER DETECTION AND PROGNOSIS

项目3，一个新的SPORE项目，目前利用发展研究计划的支持启动 SPORE将利用最先进的Bruker ClinProtTM Ultraflexll 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 肺癌患者和对照组的SPORE累积。首先，我们将开发一组蛋白质组学MS 在血清中可重复检测的特征以及已知血清相关分析物的优化组 包括细胞因子、趋化因子、生长/血管生成因子和受体，以及肺 特异性生物标志物，以提供肺癌的稳健检测和区分。该组合 MS/LabMAP（R）血清蛋白质组学检测和预测肺癌模型将在 与范德比尔特肺孢子合作的独立病例/对照血清系列，以及 在UPCI SPORE PLuSS队列中筛查CT检测的肺癌。改良的MS/ LabMAP（R）面板 和预测模型将在前瞻性收集的一系列血清样本中进行测试，这些样本来自 PLuSS高风险子队列，随后在研究期间被诊断为新发CT检测肺癌 5年积极跟进。为了测试这种蛋白质组学方法预测肺癌复发的能力， SPORE临床核心将前瞻性随访UPCI病例系列， 进展和生存。基线MALDI-TOF-MS蛋白质组图谱和MS/LabMAP（R）面板将 然后进行评估并构建模型来预测这些临床结果。预测复发 然后将在范德比尔特肺癌孢子病例中测试模型。最后，在实现这些目标的同时， 将使用一套用于肽/蛋白质鉴定的诊断MS特征（“峰”）进行研究， 用于肺癌生物标志物发现的生物化学富集/分级分离和MS分析方法。的 项目3的翻译目标是开发MS/LabMAP（R）血清谱和预测算法， 为临床症状或放射学检查结果可疑的患者提供更好的诊断 肺癌;通过鉴定MS/LabMAP（R）血清谱来提高肺癌的早期检测， 在通过筛选CT临床诊断为肺恶性肿瘤之前的高风险受试者;以及 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.