Integrated Molecular, Cellular, and Imaging Characterization of NLST detected lung cancer

NLST 检测肺癌的综合分子、细胞和成像特征

• 批准号: 10415430
• 负责人: DENISE R. ABERLE
• 金额: $ 15.6万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415430
• 关键词: Address; Aggressive Clinical Course; Aggressive behavior; Alleles; Behavior; Biological; Cells; Clinical; Clinical Management; DNA; Development; Effectiveness; Funding; Genes; Genomics; Goals; Health Policy; Image; Immune; Immunofluorescence Immunologic; Individual; Indolent; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Medicare; Modeling; Molecular; Mutation; Outcome; Patients; Phenotype; Preventive service; Research; Resected; Role; Sampling; Sea; Smoker; Somatic Mutation; Specimen; Third-Party Payer; Thoracic Radiography; Tissue Microarray; Tissue Stains; Tissues; Tumor Biology; X-Ray Computed Tomography; base; biobank; cancer diagnosis; cellular imaging; clinical decision-making; clinical heterogeneity; computed tomography screening; exome sequencing; genomic data; high risk; low dose computed tomography; lung cancer screening; mortality; new therapeutic target; novel; personalized management; precision medicine; screening; tumor; tumor-immune system interactions

PROJECT SUMMARY/ABSTRACT The landmark NLST demonstrated a 20% mortality reduction in lung cancer in individuals who underwent low dose computed tomography (LDCT) screening relative to plain chest radiography. The results of the NLST have resulted in a sea change in US health policy, such that third party payers and Medicare now provide LDCT screening as a preventive service benefit in eligible, high risk smokers. Understanding the factors underlying tumor indolence or aggression that result in heterogeneous clinical outcomes, may facilitate clinical decision making in the context of lung cancer screening and thereby greatly increase its effectiveness. We hypothesize that the mutational landscape of screen-detected lung cancers is an important contributor to their indolence or aggressiveness. To address this hypothesis we will take advantage of the comprehensively annotated NLST biorepository. Whole exome sequencing (WES) of the previously collected NLST samples will be performed to determine the genomic features that distinguish between screen-detected indolent and aggressive lung tumors that result in heterogeneous clinical outcomes. Samples from 110 patients with aggressive cancers and 494 with indolent cancers along with matching reference tissues will be assessed. By utilizing WES, we will be able to identify the impact of genes not previously associated with lung cancer as well as novel alleles of genes with known roles in lung cancer. This will be the first comprehensive genomic characterization of aggressive and indolent lung cancers diagnosed in the course of a lung cancer screening trial. The detailed genomic and imaging-based characterization of screen-detected tumors will ultimately impact clinical management of those cancers. Through separate funding, we will also integrate the genomic data obtained through this research with the tumor immune microenvironment (as characterized by multiplex immunofluorescence analysis of the same specimens) and CT imaging features to build integrated, multiparametric models of tumor biology that can be used to predict the biological behavior of lung cancers in the screening setting.

项目摘要/摘要 具有里程碑意义的NLST显示出较低的个体肺癌死亡率降低了20％ 剂量计算机断层扫描（LDCT）筛选相对于普通的胸部射线照相。 NLST的结果 已经导致了美国卫生政策的变化，因此第三方付款人和医疗保险现在提供 LDCT筛选是预防服务的好处，可在合格的高风险吸烟者中受益。了解因素 导致异质临床结果的潜在肿瘤粘性或攻击性，可能有助于临床 在肺癌筛查的背景下做出决策，从而大大提高了其有效性。我们 假设筛查肺癌的突变景观是他们的重要因素 懒惰或侵略性。为了解决这一假设，我们将全面利用 注释的NLST生物座。先前收集的NLST样品的整个外显子组测序（WES）将 执行以确定区分筛查的懒惰和 侵袭性的肺部肿瘤导致异质临床结果。来自110例患者的样本 将评估侵略性癌症和494种具有惰性癌症以及匹配参考组织的494。经过 利用WES，我们将能够确定以前与肺癌不相关的基因的影响 作为在肺癌中具有已知作用的基因的新等位基因。这将是第一个全面的基因组 在肺癌筛查过程中诊断出的侵略性和懒惰的肺癌的表征 审判。筛选肿瘤的详细基因组和基于成像的表征最终将 影响这些癌症的临床管理。通过单独的资金，我们还将整合基因组 通过肿瘤免疫微环境通过这项研究获得的数据（以多重为特征 对同一标本的免疫荧光分析）和CT成像特征，以构建集成的， 肿瘤生物学的多参数模型，可用于预测肺癌的生物学行为 筛选设置。

项目成果

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• DOI: 10.1615/critrevoncog.v20.i5-6.150
• 发表时间: 2015
• 期刊: Critical reviews in oncogenesis
• 作者: Fontebasso Y;Dubinett SM
• 通讯作者: Dubinett SM

CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA.

• DOI: 10.1186/s13059-017-1191-5
• 发表时间: 2017-03-24
• 期刊: Genome biology
• 影响因子: 12.3
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Immunosurveillance and Regression in the Context of Squamous Pulmonary Premalignancy.

• DOI: 10.1158/2159-8290.cd-20-1087
• 发表时间: 2020-10
• 期刊: Cancer discovery
• 影响因子: 28.2
• 作者: Krysan K;Tran LM;Dubinett SM
• 通讯作者: Dubinett SM

Understanding the mechanisms of immune-evasion by lung cancer in the context of chronic inflammation in emphysema.

了解肺气肿慢性炎症背景下肺癌免疫逃避的机制。

• DOI: 10.21037/jtd.2019.01.22
• 发表时间: 2019
• 期刊: Journal of thoracic disease
• 影响因子: 2.5
• 作者: Salehi-Rad,Ramin;Dubinett,StevenM
• 通讯作者: Dubinett,StevenM

Pathologic and gene expression comparison of CT- screen detected and routinely detected stage I/0 lung adenocarcinoma in NCCN risk-matched cohorts.

• DOI: 10.1016/j.ctarc.2021.100486
• 发表时间: 2021
• 期刊: Cancer treatment and research communications
• 作者: Burks EJ;Zhang J;Sullivan TB;Shi X;Sands JM;Regis SM;McKee BJ;McKee AB;Zhang S;Liu H;Liu G;Spira A;Beane J;Lenburg ME;Rieger-Christ KM
• 通讯作者: Rieger-Christ KM