Integrated Molecular, Cellular, and Imaging Characterization of Screen-Detected Lung Cancer

屏幕检测肺癌的分子、细胞和影像学综合表征

• 批准号: 10253429
• 负责人: DENISE R. ABERLE
• 金额: $ 62.49万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-16 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10253429
• 关键词: Academic Medical Centers; Aggressive Clinical Course; Aggressive behavior; Archives; Biological; Biological Markers; Biological Response Modifiers; Biopsy; Boston; California; Caring; Cells; Characteristics; Clinical; Clinical Data; Clinical Management; Collection; Data; Development; Discrimination; Disease; Effectiveness; Equilibrium; Excision; Expression Profiling; Funding; Gene Expression; Gene Expression Profile; Goals; Heterogeneity; Image; Immune; Indolent; Inflammation Mediators; Investigation; Laboratories; Lesion; Los Angeles; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Molecular; Molecular Analysis; Mutation; Nodule; Outcome; Pathogenesis; Pathway interactions; Patients; Phenotype; Precision therapeutics; Prognostic Marker; Public Health; Sample Size; Semantics; Somatic Mutation; Specimen; Systems Analysis; Tissue Banks; Tissues; Translating; Tumor Tissue; Universities; Ursidae Family; Woman; base; biobank; cancer risk; cellular imaging; clinical decision-making; cohort; design; driver mutation; exome sequencing; insight; low-dose spiral CT; lung cancer screening; mRNA sequencing; men; mortality; multidisciplinary; new therapeutic target; personalized management; prospective; public health relevance; quantitative imaging; screening; screening policy; translational research program; tumor; tumor microenvironment

 DESCRIPTION (provided by applicant): The University of California at Los Angeles - Boston University Molecular Characterization Laboratory (UCLA- BU MCL) is a multidisciplinary, translational research program designed to enhance our understanding of the molecular, cellular and imaging features distinguishing indolent from aggressive lung cancers in screen- detected and non-screen-detected clinical settings. The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The benefits of screening, however, must be reconciled with its potential harms, including high false positive rates and the potential for overdiagnosis. Our broad goal is to distinguish indolent from aggressive lesions by interrogating the molecular, microenvironment and imaging features that are associated with clinical outcomes. This global approach brings all aspects of these investigations to bear on our understanding of the molecular pathogenesis of early stage lung cancer. These results will be translated to the clinical management of screen-detected lung cancer. Understanding the factors underlying tumor indolence or aggression that result in heterogeneous clinical outcomes will facilitate clinical decision making in the context of lung cancer screening, increase screening effectiveness and ultimately drive care pathways. We hypothesize that the pathways underlying heterogeneity in screen-detected lung cancers will be revealed by analysis of molecular (whole exome and mRNA sequencing), microenvironment (immune and inflammatory mediators) and imaging characteristics (semantic and quantitative features) of screen- detected lesions. The specific aims are: Aim 1: Identify molecular, cellular and imaging profiles that distinguish screen-detected from non-screen- detected lung cancers. Aim 2: Identify molecular, cellular and imaging profiles that distinguish screen-detected lung cancers with indolent versus aggressive clinical courses from the NLST. Aim 3: Confirm and refine molecular, cellular and imaging profiles that distinguish screen-detected lung cancers with indolent versus aggressive clinical courses from a prospectively collected screening cohort. Cases will derive from the NLST biorepository, DECAMP cohorts and a University of California (UC) state-wide initiative involving the five UC academic medical centers that are establishing a common screening policy and platform that involves the collection and archiving of clinical, imaging, and tissue specimens.

 描述(由申请人提供)：加州大学洛杉矶分校-波士顿大学分子特征实验室(UCLA-BU MCL)是一个多学科的转化性研究计划，旨在加强我们对分子、细胞和成像特征的理解，以区分屏幕检测和非屏幕检测的临床环境中惰性肺癌和侵袭性肺癌。国家肺部筛查试验(NLST)提供了令人信服的证据，证明使用低剂量螺旋CT(LDCT)进行肺癌筛查可以降低肺癌死亡率。然而，筛查的好处必须与其潜在的危害相协调，包括高假阳性率和过度诊断的可能性。我们的广泛目标是通过询问与临床结果相关的分子、微环境和成像特征来区分惰性和侵袭性损害。这种全球性的方法使这些研究的方方面面都与我们对早期肺癌分子发病机制的理解有关。这些结果将转化为筛查发现的肺癌的临床治疗。了解导致临床结果不同的肿瘤惰性或侵略性的因素将有助于在肺癌筛查的背景下进行临床决策，提高筛查效率，并最终推动护理路径。我们假设，通过对分子(整个外显子组和mRNA测序)、微环境(免疫和炎症介质)和成像特征(语义和定量特征)的分析，将揭示筛查发现的肺癌的异质性的潜在途径。具体目标是：目标1：确定分子、细胞和成像特征，以区分筛查发现和未筛查发现的肺癌。目的2：确定分子、细胞和影像特征，以区分NLST筛查发现的肺癌的惰性和侵袭性临床过程。目的3：确认和提炼分子、细胞和影像资料，从前瞻性收集的筛查队列中区分筛查发现的肺癌的惰性和侵袭性临床病程。病例将来自NLST生物存储库、DeCamp队列和加州大学(UC)全州范围内的一项倡议，该倡议涉及加州大学的五个学术医疗中心，这些中心正在建立一个共同的筛查政策和平台，涉及临床、成像和组织标本的收集和归档。