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.