Autoantibodies in NSCLC as Markers for Disease

NSCLC 中的自身抗体作为疾病标志物

• 批准号: 7259580
• 负责人: Edward A. Hirschowitz
• 金额: $ 25.64万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-05 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7259580
• 关键词: Address; Age; Antibodies; Appearance; Autoantibodies; Bacteriophages; Benign; Biological Assay; Biological Markers; Blinded; Blood Tests; Cancer Detection; Cancer Patient; Chest; Clinical; Clinical Research; Complement; Complementary DNA; Detection; Diagnosis; Diagnostic Procedure; Disease; Disease Marker; Disease Outcome; Dose; Early Detection Research Network; Early Diagnosis; Environment; Equipment and supply inventories; Glass; Heterogeneity; High-Risk Cancer; Imaging Techniques; Incidence; Individual; Kentucky; Lesion; Libraries; Lung; Lung diseases; Lung nodule; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Measures; Morbidity - disease rate; Non-Malignant; Non-Small-Cell Lung Carcinoma; Patients; Performance; Phase; Plasma; Population; Positron-Emission Tomography; Protein Array; Proteins; Public Health; Pulmonary Coin Lesion; Rate; Receiver Operating Characteristics; Reporting; Research Personnel; Risk; Role; Sampling; Scanning; Screening procedure; Selection Criteria; Sensitivity and Specificity; Serological; Slide; Smoking History; Staging; Testing; Tumor Antibodies; Tumor Markers; Validation; X-Ray Computed Tomography; base; cancer diagnosis; case control; clinical application; cost; cost effectiveness; design; follow-up; improved; mortality; performance tests; programs; tool; tumor

DESCRIPTION (provided by applicant): The use of only age and smoking history as selection criteria in population-based CT screening trials has afforded a low yield of cancer detection at significant cost. Moreover, the routine identification of indeterminate pulmonary nodules during CT screening often requires additional workup, magnifying the cost and adding potential morbidity from related interventional diagnostic procedures. We have developed a blood test for NSCLC that may address these limitations when integrated into the early detection paradigm. Specifically, we exploited the expansive autoantibody repertoire of lung cancer patients to develop a multi-marker assay that compensates for NSCLC heterogeneity. Capture proteins were selected from cDNA tumor libraries using antibodies in patient plasma and in turn used to measure tumor-associated antibodies as markers of disease. Fluorescent microarray was adapted as a platform to accommodate a multiple marker approach. Individual markers were ranked by statistical differences between case and control samples, and Receiver Operating Characteristic (ROC) was used to statistically define an optimal combination of those markers with high discriminatory value. Classifiers for a combined marker set were then built on known case and control samples and used to predict disease in available samples. Performance results indicate excellent potential for clinical utility. Having successfully completed the biomarker discovery phase of this project, the current proposal has three primary objectives: 1) To evaluate assay performance for established lung cancer diagnosed in an expanded clinical population 2) to define a role for this assay in management of radiographically identified indeterminate pulmonary nodules independent of a screening study, and 3) to confirm results that indicate this marker set may detect cancer and predict the onset of NSCLC prior to radiographic detection in a screened population. Relevance to Public Health. A blood test for lung cancer could improve the capability and cost- effectiveness of early detection as a viable strategy for reducing mortality from this disease.

描述（由申请人提供）：在基于人群的CT筛查试验中，仅使用年龄和吸烟史作为选择标准，这使得癌症检测的产量低，成本高。此外，在CT筛查中常规识别不确定的肺结节往往需要额外的检查，这增加了成本，并增加了相关介入诊断程序的潜在发病率。我们已经开发了一种非小细胞肺癌的血液检测方法，当整合到早期检测范式中时，可能会解决这些局限性。具体来说，我们利用肺癌患者广泛的自身抗体库来开发一种多标记分析，以补偿非小细胞肺癌的异质性。利用患者血浆中的抗体从cDNA肿瘤文库中选择捕获蛋白，然后用于测量作为疾病标志物的肿瘤相关抗体。荧光微阵列被适应为一个平台，以适应多标记方法。根据病例和对照样本之间的统计差异对个体标记进行排序，并采用受试者工作特征（Receiver Operating Characteristic， ROC）统计确定具有高判别值的标记的最佳组合。然后在已知病例和对照样本上建立组合标记集的分类器，并用于预测可用样本中的疾病。性能结果显示其具有良好的临床应用潜力。在成功完成该项目的生物标志物发现阶段后，目前的提案有三个主要目标：1)评估在扩大的临床人群中诊断出的已确诊肺癌的检测性能；2)确定该检测在独立于筛查研究的放射学鉴定的不确定肺结节管理中的作用；3)确认结果表明该标记集可以在筛查人群中检测出癌症并预测非小细胞肺癌的发病。与公共卫生相关。肺癌的血液检测可以提高早期检测的能力和成本效益，作为降低这种疾病死亡率的可行策略。