Blood Biomarkers for Lung Cancer Screening Risk Assessment, and Early Detection

用于肺癌筛查风险评估和早期检测的血液生物标志物

基本信息

批准号：
8890488
负责人：
Ayumu Taguchi
金额：
$ 36.6万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
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：
2015-07-13 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8890488
关键词：
Adult Age All-Trans-Retinol Annexins Autoantibodies Benign Beta Carotene Biological Assay Biological Markers Biopsy Blinded Blood Carotene Clinical Cohort Studies Colorectal Cancer Complement Data Diagnosis Diagnostic Dose Early Diagnosis Event Gender German population Goals IGFBP2 gene Image Incidence Individual Intervention Trial LAMR1 gene Logistic Regressions Lung Malignant - descriptor Malignant neoplasm of lung Malignant neoplasm of prostate Modeling Nodule Operative Surgical Procedures Participant Performance Predictive Value Probability Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Proteins Proteomics Radiation Reporting Research Design Risk Risk Assessment Risk Factors Sampling Screening for Ovarian Cancer Series Smoker Smoking History Specificity Specimen Staging Stratification TIMP1 gene Testing Time Training Validation Visit WFDC2 gene Weight X-Ray Computed Tomography base cancer risk clinical application cohort cost efficacy trial follow-up high risk imaging biomarker low-dose spiral CT lung cancer screening model building mortality prospective public health relevance screening validation studies

项目摘要

DESCRIPTION (provided by applicant): The National Lung Screening Trial (NLST) reported that low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in adults at high risk for lung cancer. Despite these significant results, there are major concerns regarding lung cancer screening with LDCT. They include high false positivity, cost, and radiation exposure. Blood-based markers are a promising and attractive approach to complement LDCT because of the potential to identify those subjects that may be at increased risk of developing lung cancer, or that may be harboring early and potentially curable lung cancer, or that need to undergo further work-up for their indeterminate nodules. We have identified through a series of discovery and initial validation studies, a set of biomarker candidates with potential for early detection. They include seven protein biomarkers (LRG1, WFDC2, pro-SFTPB, LCN2, IGFBP2, TIMP1, and ANGPTL3) and autoantibodies against Annexin 1, 14-3-3 theta, and LAMR1. As a proof of principle, one of these candidates, pro-SFTPB, was further tested in the Pan- Canadian Early Detection of Lung Cancer Study (PanCan), which consists of 2,537 subjects with high risk of lung cancer with 113 subjects found to have lung cancer. Pro-SFTPB was significantly and independently associated with lung cancer and added to lung cancer prediction with established risk factors. The major goal of our proposal is to increase the efficiency of LDCT. The specific objectives are to develop, refine and validate blood-based biomarkers for: (1) risk assessment of current smokers and former smokers to determine who needs LDCT screening; (2) early detection of lung cancer in current and former smokers based on incidence lung cancer cases; and (3) reduction of the false positive rate of LDCT and increase the positive predictive value of LDCT. To achieve these objectives, we have obtained access to pre-diagnostic samples from cohort studies including the Beta-Carotene and Retinol Efficacy Trial (CARET) and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), and access to two independent screening studies, the PanCan and the German Lung Cancer Screening Intervention Trial (LUSI). Validation studies will proceed in a blinded fashion with combination rules defined in training sets that fit the intended clinical applications.

描述（由申请人提供）：国家肺部筛查试验 (NLST) 报告称，低剂量计算机断层扫描 (LDCT) 筛查可将肺癌高危成人的肺癌死亡率降低 20%，尽管取得了这些显着结果，但仍有重大进展。 LDCT 肺癌筛查的担忧包括高假阳性率、成本和辐射暴露，基于血液的标记物是一种有前途且有吸引力的补充 LDCT 的方法，因为它有可能识别那些可能面临更高风险的受试者。我们通过一系列发现和初步验证研究确定了一组具有潜在潜力的候选生物标志物。它们包括七种蛋白质生物标志物（LRG1、WFDC2、pro-SFTPB、LCN2、IGFBP2、TIMP1 和 ANGPTL3）和针对膜联蛋白 1 的自身抗体， 14-3-3 theta 和 LAMR1 作为原理证明，其中一个候选者 pro-SFTPB 在泛加拿大肺癌早期检测研究 (PanCan) 中进行了进一步测试，该研究由 2,537 名具有高水平的受试者组成。发现 113 名受试者患有肺癌，Pro-SFTPB 的风险与肺癌显着且独立相关，并添加到已确定的风险因素的肺癌预测中。 LDCT 的具体目标是开发、完善和验证基于血液的生物标志物，用于：(1) 对当前吸烟者和前吸烟者进行风险评估，以确定谁需要 LDCT 筛查；(2) 在当前和前吸烟者中早期发现肺癌。基于肺癌病例的发病率；(3) 降低 LDCT 的假阳性率并提高 LDCT 的阳性预测价值为了实现这些目标，我们获得了来自队列研究的预诊断样本，包括 β-胡萝卜素。和视黄醇功效试验 (CARET) 和前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验 (PLCO)，以及两项独立筛查研究：PanCan 和德国肺癌筛查干预验证研究 (LUSI) 将在一项研究中进行。盲目时尚，在训练集中定义了适合预期临床应用的组合规则。