New Diagnostic Assay for Early Detection of Lung Cancer

早期发现肺癌的新诊断方法

• 批准号: 7175802
• 负责人: Feng Jiang
• 金额: $ 12.77万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7175802
• 关键词: bioinformatics; biomarker; biomedical automation; biotechnology; clinical research; cytogenetics; diagnosis design /evaluation; diagnosis quality /standard; early diagnosis; fluorescent dye /probe; fluorescent in situ hybridization; genetic screening; histopathology; human subject; lung neoplasms; microarray technology; neoplasm /cancer diagnosis; neoplasm /cancer epidemiology; neoplasm /cancer genetics; respiratory epithelium

DESCRIPTION (provided by applicant): Early diagnosis of lung cancer may reduce the mortality associated with it. We have demonstrated that multicolor-fluorescence in situ hybridization with chromosomal probes is more sensitive in detecting lung cancer cells than conventional cytologic studies are. We precisely defined genomic signatures in primary lung cancer and developed specific probes for these signatures. We also obtained biologic samples and corresponding epidemiologic and clinical data from patients with lung cancer under an Institutional Review Board approved protocol. We hypothesize that these signatures constitute biomarkers and that an in situ strategy with a panel of specific probes for the genomic signatures will be sufficiently sensitive and specific to detect early neoplasia of the lung. Based on the principle of in situ hybridization, taking advantage of array techniques, we propose to develop an innovative in situ array that will allow simultaneous measurement of these key tumor-specific genetic changes and that can be simply applied to easily accessible surrogate specimens. We will first evaluate the potential biomarkers by dual-color fluorescence in situ hybridization with lung tissue microarrays to identify a set of probes that provide the greatest overall sensitivity and specificity for detection of lung cancer cells. We will then develop an in situ genomic DNA array: a glass coverslip to which a cocktail of these probes, labeled with multicolor fluorochromes, will be bound. We will test the assay with sputum and oral brushings and lung tumor tissue specimens from consecutive patients with lung cancer who had undergone thoracotomy and compare these data with clinical covariates to determine the assay's diagnostic ability with surrogate tissues. Finally, we will combine the assay with an automated dot-counting system to develop a reliable, cost-effective, rapid genetic test for lung carcinogenesis. This study should result in the first in situ-based assay consisting of multiple specific genetic probes that can be employed for routine diagnosis with surrogate materials. This novel strategy will have substantial implications for large-scale population-based molecular epidemiologic studies and therapeutic interventions. It will also have great application for the diagnosis and staging of other types of cancer when combined with other appropriate tumor-specific genes. This project will be multidisciplinary, incorporating epidemiology, molecular biology, cytogenetics, pathology, bioinformatics, and statistics.

描述（由申请人提供）：肺癌的早期诊断可以降低与其相关的死亡率。我们已经证明，使用染色体探针的多色荧光原位杂交在检测肺癌细胞方面比传统的细胞学研究更敏感。我们精确定义了原发性肺癌的基因组特征，并为这些特征开发了特异性探针。我们还根据机构审查委员会批准的方案从肺癌患者中获取了生物样本以及相应的流行病学和临床数据。我们假设这些特征构成生物标志物，并且使用一组针对基因组特征的特异性探针的原位策略将具有足够的敏感性和特异性来检测肺部的早期肿瘤。基于原位杂交的原理，利用阵列技术，我们建议开发一种创新的原位阵列，该阵列将允许同时测量这些关键的肿瘤特异性遗传变化，并且可以简单地应用于易于获取的替代样本。我们将首先通过双色荧光原位杂交与肺组织微阵列评估潜在的生物标志物，以确定一组可为肺癌细胞检测提供最高总体灵敏度和特异性的探针。然后，我们将开发一个原位基因组 DNA 阵列：一个玻璃盖玻片，上面将结合这些用多色荧光染料标记的探针混合物。我们将使用来自接受开胸手术的连续肺癌患者的痰液、口腔刷牙和肺肿瘤组织标本来测试该测定，并将这些数据与临床协变量进行比较，以确定该测定对替代组织的诊断能力。最后，我们将将该检测与自动点计数系统结合起来，开发一种可靠、经济高效、快速的肺癌基因检测方法。这项研究应该产生第一个由多个特定基因探针组成的原位测定，可用于替代材料的常规诊断。这种新颖的策略将对大规模基于人群的分子流行病学研究和治疗干预产生重大影响。当与其他适当的肿瘤特异性基因结合时，它对于其他类型癌症的诊断和分期也将有很大的应用。该项目将是多学科的，包括流行病学、分子生物学、细胞遗传学、病理学、生物信息学和统计学。