Novel Protein Risk Markers for Lung Cancer

肺癌的新型蛋白质风险标志物

• 批准号: 9188094
• 负责人: FREDERICA P PERERA
• 金额: $ 18.42万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9188094
• 关键词: Age; All-Trans-Retinol; Beta Carotene; Biological Assay; Biological Markers; Blinded; Blood; Blood specimen; Cancer Etiology; Carotene; Cessation of life; Chemoprevention; Clinical; Cohort Studies; Collection; Complement; DNA; Data Analyses; Detection; Diagnosis; Diagnostic; Disease; Early Diagnosis; Early identification; Enrollment; Enzyme-Linked Immunosorbent Assay; Enzymes; Future; Goals; Health; Immune; Individual; Life Style; Link; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measurable; Measures; MicroRNAs; Modality; Mutate; Non-Small-Cell Lung Carcinoma; Performance; Physicians; Plasma; Premalignant Change; Process; Proteins; Proteomics; Pulmonary Surfactant-Associated Protein B; Radiation exposure; Risk; Risk Assessment; Risk Marker; Sampling; Set protein; Signal Transduction; Smoking; Specificity; Survival Rate; Technology; Testing; Time; Variant; Woman; Work; base; biomarker panel; candidate marker; case control; clinical Diagnosis; cohort; cost; diagnostic biomarker; early detection biomarkers; efficacy trial; follow-up; improved; individualized medicine; low-dose spiral CT; lung cancer screening; lung small cell carcinoma; men; metabolomics; multiple reaction monitoring; nanoparticle; novel; novel strategies; personalized medicine; protein biomarkers; public health relevance; screening; tool; validation studies

 DESCRIPTION (provided by applicant): Protein markers originating in the lung and measurable in the circulating plasma have the potential to complement low-dose computed tomography (LDCT) within a comprehensive risk assessment and screening process. Based on integrative analysis of data from several quantitative plasma profiling platforms (glycomics, metabolomics, immunomics, and proteomics), we have previously identified a set of circulating protein biomarker candidates that, in initial validation studies, had the ability to discriminate between pre-diagnostic plasmas of lung cancer cases from those of control subjects in the Beta-Carotene and Retinol Efficacy Trial (CARET) cohort. The main goal of our proposed study is to determine if the candidate biomarkers identified in the CARET cohort also can detect cancer before clinical diagnosis in the Physicians' Health Study (PHS) cohort. A unique feature of the PHS cohort is the long duration of follow-up, with a lapse of 0.5 to 25 years between baseline blood collection and diagnosis of cases. This allows us to determine the performance of the markers in relation to time to diagnosis; i.e., whether they are most useful as markers of risk, signaling pre-malignant changes, or as early detection markers that signal the emergence of malignancy. The primary aim of this study is to validate a panel of previously identified candidate protein biomarkers for lung cancer by testing these biomarkers in a set of blinded samples drawn from the PHS cohort. Baseline plasma samples drawn at enrollment will be analyzed for each candidate protein biomarker using an enzyme-linked immune-sorbent assay (ELISA). We will then compare cases (n=182) and controls (n=325), matched on age, smoking, and duration of follow-up, with respect to the biomarkers, individually and in combination (panel). The second aim of this study is to determine the biomarker panels appropriate for each of two modalities: 1) risk assessment, in which we will determine a panel with high sensitivity to predict lung cancer > 8 years before diagnosis and help guide decisions regarding the need for follow up with LDCT; and 2) early detection, in which we will determine a panel with high specificity to predict lung cancer < 8 years before diagnosis as a complement to LDCT, which is costly and has very high sensitivity but low specificity. The third aim of this study is to utiliz nanoparticle technology to develop sensitive, low-cost multiple reaction monitoring (MRM) assays for the application of validated biomarkers in the clinical setting. Conclusion: If validated, a panel of protein biomarkers that can be feasibly measured in blood will offer a new tool to assess risk and/or screen for early lung cancer so that chemoprevention, lifestyle changes, and treatment measures can be applied as appropriate, reducing the burden of lung cancer.

 描述（由申请人提供）：源自肺部且可在循环血浆中测量的蛋白质标记物有可能在全面的风险评估和筛查过程中补充低剂量计算机断层扫描（LDCT）。基于对多个定量血浆分析平台（糖组学、代谢组学、免疫组学和蛋白质组学）数据的综合分析，我们之前已经确定了一组循环蛋白质生物标志物候选物，在初步验证研究中，这些候选物能够区分肺癌病例的诊断前血浆与β-胡萝卜素和视黄醇功效试验中对照受试者的血浆 （CARET）队列。 我们提出的研究的主要目标是确定 CARET 队列中确定的候选生物标志物是否也可以在医生健康研究 (PHS) 队列中进行临床诊断之前检测癌症。 PHS队列的一个独特特征是随访时间长，从基线采血到病例诊断之间相隔0.5至25年。这使我们能够确定标记物与诊断时间相关的性能；即，它们是否最有用作为风险标记、发出癌前变化信号，或作为发出恶性肿瘤出现信号的早期检测标记。 本研究的主要目的是通过在从 PHS 队列中抽取的一组盲样样本中测试这些生物标志物来验证一组先前确定的肺癌候选蛋白质生物标志物。将使用酶联免疫吸附测定 (ELISA) 分析入组时抽取的基线血浆样本中的每个候选蛋白质生物标志物。然后，我们将根据生物标志物单独和组合比较病例 (n=182) 和对照 (n=325)，匹配年龄、吸烟情况和随访时间（面板）。 本研究的第二个目的是确定适合两种模式的生物标志物组：1）风险评估，其中我们将确定一个具有高灵敏度的组，以在诊断前预测> 8年的肺癌，并帮助指导有关是否需要进行 LDCT 随访的决策； 2) 早期检测，其中我们将在诊断前确定一个具有高特异性的面板来预测肺癌 < 8 年，作为 LDCT 的补充，LDCT 成本高昂，灵敏度非常高，但特异性较低。 本研究的第三个目标是利用纳米颗粒技术开发灵敏、低成本的多反应监测 (MRM) 检测方法，以便在临床环境中应用经过验证的生物标志物。 结论：如果经过验证，一组可以在血液中可行测量的蛋白质生物标志物将提供一种新的工具来评估早期肺癌的风险和/或筛查，以便可以适当地应用化学预防、生活方式的改变和治疗措施，从而减轻肺癌的负担。