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.

项目概要/摘要 具有里程碑意义的 NLST 证明，接受低剂量治疗的个体肺癌死亡率可降低 20% 剂量计算机断层扫描 (LDCT) 筛查相对于胸部平片检查。 NLST 的结果 导致美国医疗政策发生巨大变化，第三方付款人和医疗保险现在提供 LDCT 筛查作为符合资格的高风险吸烟者的预防服务福利。了解因素 潜在的肿瘤惰性或攻击性导致异质的临床结果，可能有助于临床 肺癌筛查背景下的决策，从而大大提高其有效性。我们 假设屏幕检测到的肺癌的突变情况是其发生的重要因素 懒惰或攻击性。为了解决这个假设，我们将综合利用 带注释的 NLST 生物样本库。先前收集的 NLST 样本的全外显子组测序 (WES) 将 进行以确定区分屏幕检测到的惰性和惰性的基因组特征 侵袭性肺部肿瘤导致不同的临床结果。来自 110 名患者的样本 第 494 章经过 利用 WES，我们将能够识别以前与肺癌无关的基因的影响 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 肺癌筛查过程中诊断出的侵袭性和惰性肺癌的特征 审判。筛选检测到的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。通过单独的资助，我们还将整合基因组 通过本研究获得的肿瘤免疫微环境数据（以多重特征为特征） 相同样本的免疫荧光分析）和 CT 成像功能，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

Drug Development for Metastasis Prevention.

• DOI: 10.1615/critrevoncog.v20.i5-6.150
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• 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