A Genetic Test for Lung Cancer Early Detection

肺癌早期检测的基因检测

• 批准号: 7475337
• 负责人: Feng Jiang
• 金额: $ 7.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-04 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7475337
• 关键词: Adoption; American Association of Cancer Research; Biological Markers; Bronchoscopy; Cancer Patient; Clinical; Cohort Studies; Color; Complement; DNA Probes; Data; Databases; Detection; Diagnosis; Diagnostic; Diagnostic Procedure; Diagnostic tests; Disease; Dyes; Early Diagnosis; Engineering; Fluorescence; Fluorochrome; Future; Genetic; Genetic Techniques; Genetic screening method; Genome; Genomics; Goals; Grant; In Situ; Invasive; Knowledge; Label; Liquid substance; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Microarray Analysis; Molecular Genetics; Mutation; Nanotechnology; Numbers; Patients; Process; Quantum Dots; Rate; Relative (related person); Research; Research Design; Resources; Sampling; Secure; Sensitivity and Specificity; Series; Signal Transduction; Smoker; Sputum; Sputum Cytology Screening; Staging; Technology; Testing; Thoracic Radiography; Translating; Woman; Work; anticancer research; base; cancer cell; case control; clinical Diagnosis; clinical application; clinically significant; comparative genomic hybridization; design; genetic analysis; improved; innovation; lung cancer screening; men; mortality; nanoprobe; nanoscale; news; non-smoker; prospective; size

DESCRIPTION (provided by applicant): Lung cancer is the number one cancer killer for men and women in the USA. The ability to detect lung cancer at its early, curable stages will reduce the mortality and is thus an important clinical goal. Toward this goal, using genome-wide microarray-based comparative genomic hybridization analysis of primary lung tumors, we have identified a set of genetic signatures that can be detected in sputum and provided potential biomarkers for the early detection of lung cancer (Clin Cancer Res, 2007, 15 and AACR breaking News). We have also developed an in situ mini-chip consisting of a panel of probes for simultaneously measuring multiple genetic changes in a single test. However, the application of the potential genetic biomarkers and test in the clinical settings is limited by the probes that are labeled with organic dyes, because the conventional fluorochromes fade fast and show blurry signals, and thus reduce the sensitivity of the biomarkers in the detection of cancer cells. The newly developed quantum dots (QDs) feature intense and stable fluorescence, and provide a promising approach for effectively detecting molecular genetic targets. The objective of this R03 exploratory study is to develop a diagnostic test that can reliably detect genetic biomarkers using sputum for the early detection of lung cancer. We propose to 1) develop a nanogenetic test by incorporating the most optimum fluorescent QDs into the probes of the genetic signatures and integrating the nanoprobes into the in situ mini-chip, 2) determine diagnostic utility of the nanogenetic test for the early detection of lung cancer in sputum samples from 83 patients with stage I lung cancer and 83 cancer-free heavy smokers and 83 nonsmokers. At the conclusion of this study, we expect to develop a genetic approach for effectively detecting the biomarker panel in sputum that can be used for the early detection of lung cancer with high sensitivity. This exploratory R03 grant will set the stage for future large-scale cohort studies designed to validate its utility for adoption in routine clinical settings. Resources that will contribute towards our objective include a bank of well-characterized sputum samples with comprehensive clinical and cytopathologic database.

描述（由申请人提供）： 肺癌是美国男性和女性的头号癌症杀手。在早期可治愈阶段检测肺癌的能力将降低死亡率，因此是一个重要的临床目标。为了实现这一目标，使用基于全基因组微阵列的原发性肺肿瘤的比较基因组杂交分析，我们已经鉴定了一组可以在痰中检测到的遗传特征，并为肺癌的早期检测提供了潜在的生物标志物（Clin Cancer Res，2007，15和AACR breaking News）。我们还开发了一种由一组探针组成的原位微型芯片，用于在一次测试中同时测量多种遗传变化。然而，潜在的遗传生物标志物和检测在临床环境中的应用受到有机染料标记的探针的限制，因为常规荧光染料褪色快且显示模糊的信号，从而降低了生物标志物在检测癌细胞中的灵敏度。新开发的量子点（QDs）具有强而稳定的荧光，为有效检测分子遗传靶标提供了一种有前途的方法。本R03探索性研究的目的是开发一种诊断测试，可以使用痰液可靠地检测遗传生物标志物，用于肺癌的早期检测。我们建议：1）通过将最优化的荧光量子点结合到基因签名的探针中并将纳米探针整合到原位微型芯片中来开发纳米遗传学测试，2）确定纳米遗传学测试在83名I期肺癌患者和83名无癌症重度吸烟者和83名非吸烟者的痰液样本中早期检测肺癌的诊断效用。在这项研究的结论，我们希望开发一种基因的方法，有效地检测痰中的生物标志物面板，可用于肺癌的早期检测具有高灵敏度。这项探索性的R03资助将为未来的大规模队列研究奠定基础，这些研究旨在验证其在常规临床环境中的实用性。有助于实现我们目标的资源包括一个具有全面临床和细胞病理学数据库的特征良好的痰液样本库。