Hybrid Plasma Markers that Complement CT Imaging for Early Lung Cancer Detection

混合血浆标记物可补充 CT 成像以进行早期肺癌检测

基本信息

批准号：
9248994
负责人：
A McGarry Houghton
金额：
$ 51.64万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9248994
关键词：
Adherence Age Age-Years Algorithms Antibodies Antigens Apoptosis Attention Autoantibodies B-Lymphocytes Benign Biological Markers Biopsy Blood Breast Cancer Etiology Cancer Histology Cancerous Caring Cells Cessation of life Characteristics Chest Chronic Obstructive Airway Disease Clinic Clinical Clinical Data Colon Colon Carcinoma Complement Complex Costs and Benefits Data Detection Diagnosis Diagnostic Dimensions Dose Enzyme-Linked Immunosorbent Assay Evaluation FDA approved Gender Guidelines Hybrids Image Immune Immunologic Markers Infiltration Lung Lung nodule Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of ovary Medical Metabolism Methods Modeling Morbidity - disease rate Multivariate Analysis Nodule Operative Surgical Procedures Pancreas Patient Care Patients Plasma Practice Guidelines Procedures Property Prostate Protein Array Proteomics Race Radiation exposure Reporting Reproducibility Research Design Rest Risk stratification Sampling Scanning Severities Smoker Smoking History Specificity Specimen Survival Rate Testing Translations Tumor-Derived Tumor-Infiltrating Lymphocytes United States Unnecessary Procedures Validation Variant X-Ray Computed Tomography aged angiogenesis base biomarker discovery biomarker panel blood-based biomarker cancer cell cancer diagnosis candidate marker cardiovascular health case control chest computed tomography clinical care cohort cost density design high risk high risk population improved lung cancer screening lung imaging malignant breast neoplasm mortality new technology outcome forecast performance tests predictive modeling programs prospective public health relevance screening standard care theories

项目摘要

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer death in the United States and worldwide. In 2013, it is estimated that there will be at least 228,000 new cases of lung cancer diagnosed and more than 159,000 deaths in the United States - approximately equal to the next four most common causes of cancer-related mortality combined (colon, breast, prostate, pancreas). The NCI-sponsored, National Lung Screening Trial (NLST) found a 20% reduction in lung cancer specific mortality in high-risk subjects screened with low-dose chest computed tomography (CT). However, 26% of CT-scans reported noncalcified nodules >4 mm while only 5% of these positive findings would actually be expected to be cancer. Analysis of several screening cohorts indicates that 25-50% of smokers >50 years of age have CT identifiable pulmonary nodules but very few of them (~2.5%) are caused by lung cancer. Current practice guidelines for pulmonary nodule evaluation call for invasive biopsy procedures depending upon the size and characteristics of the nodule and key clinical parameters (e.g., age, smoking history), raising considerable cost/benefit and morbidity/mortality considerations even in this high-risk population. Clearly there is a need for additional risk stratification for subjects that have pulmonary nodules detected by CT imaging. Discovery of viable proteomic, glycomic and/or immunological biomarkers in blood to complement CT would be especially valuable to guide clinical care. However, no plasma markers have advanced sufficiently in validation trials to be viable FDA-approved candidates. We created a high density antibody array containing 3200 different antibodies that we use to interrogate pre-diagnostic sample sets from observational trials in a nested case-control design study to evaluate proteomic, glycomic and autoantibody differences. We have shown that this novel technology is highly sensitive and reproducible. Furthermore, we have confirmed known and found new viable proteomic biomarker candidates in ovarian, breast, colon and lung cancer. Using pre-diagnostic lung cancer samples from the Cardiovascular Health Study (CHS), we found 30 proteomic, glycomic or autoantibody biomarkers that were significantly increased (p<0.002) in people that are subsequently diagnosed with lung cancer. Here, we propose to use plasma samples from 297 lung nodule positive subjects that have been screened via CT and have known cancer/nodule status (147 were cancer) to test these 30 markers and potentially discover additional candidates. We will then combine these data with CT imaging parameters and clinical data to create a risk prediction model that we will test in a similar sized prospectivly collected cohort. Our specific aims are: (1) Test the ability of putative proteomic and glycomic biomarkers to identify malignant pulmonary nodules. (2) Determine if autoantibodies present in plasma are tumor-derived and assess their utility for the detection of cancerous nodules. (3) Perform multivariate analyses of hybrid plasma biomarkers to distinguish malignant from benign nodules identified on CT chest imaging.

描述（由申请人提供）：肺癌是美国和全世界癌症死亡的主要原因。据估计，2013 年美国将有至少 228,000 例新诊断肺癌病例，超过 159,000 例死亡。州 - 大约等于癌症相关死亡的接下来四种最常见原因的总和（结肠癌、乳腺癌、前列腺癌、胰腺癌）。 (NLST) 发现，通过低剂量胸部计算机断层扫描 (CT) 筛查的高危受试者的肺癌特异性死亡率降低了 20%，然而，26% 的 CT 扫描报告非钙化结节 >4 毫米，而其中只有 5%。对几个筛查队列的分析表明，25-50% 的 50 岁以上吸烟者有 CT 可识别的肺部结节，但其中很少有阳性结果。 (~2.5%) 是由肺癌引起的。目前肺结节评估的实践指南要求根据结节的大小和特征以及关键临床参数（例如年龄、吸烟史）进行侵入性活检，这提高了相当大的成本/效益。显然，即使在这一高危人群中，也需要对通过 CT 成像检测到的肺部结节进行额外的风险分层。然而，在验证试验中，血浆标记物还没有取得足够的进展，成为 FDA 批准的可行候选者，我们创建了一个包含 3200 种不同抗体的高密度抗体阵列，用于询问预检测。 -来自嵌套病例对照设计研究中的观察试验的诊断样本集，用于评估蛋白质组、糖组和自身抗体差异。此外，我们已经证实了已知的并发现了新的可行的蛋白质组生物标志物。使用来自心血管健康研究 (CHS) 的预诊断肺癌样本，我们发现 30 种蛋白质组、糖组或自身抗体生物标志物在随后接受治疗的人群中显着增加 (p<0.002)。在这里，我们建议使用 297 名肺结节阳性受试者的血浆样本进行测试，这些受试者已通过 CT 筛查并已知癌症/结节状态（其中 147 名是癌症）。然后，我们将这些数据与 CT 成像参数和临床数据结合起来，创建一个风险预测模型，我们将在类似规模的前瞻性收集的队列中进行测试，我们的具体目标是：(1) 测试能力。 (2) 确定血浆中存在的自身抗体是否源自肿瘤，并评估其在检测癌性结节中的效用。 (3) 对混合血浆进行多变量分析。用于区分 CT 胸部成像识别的恶性结节和良性结节的生物标志物。