Tumor-specific autoantibodies for SCLC early detection

用于 SCLC 早期检测的肿瘤特异性自身抗体

• 批准号: 10299616
• 负责人: A McGarry Houghton
• 金额: $ 14.89万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-17 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10299616
• 关键词: Accounting; American; Antibodies; Antigens; Autoantibodies; Autoantigens; Biological Assay; Breast; Cancer Center; Cancer Etiology; Cancer Patient; Cessation of life; Clinic; Clinical; Colon Carcinoma; Complex; Data Set; Detection; Development; Diagnosis; Diagnostic; Disease; Early Diagnosis; Extensive Stage; Generations; Goals; Human; Hybrids; Image; Length; Lesion; Limited Stage; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Methodology; Minority; Modality; Modeling; Molecular; Neuraxis; Nodule; Non-Small-Cell Lung Carcinoma; Outcome; Ovarian; Pancreas; Paraneoplastic Syndromes; Patients; Plasma; Prevention; Process; Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; Proteins; Proteomics; Reproducibility; Sampling; Screening for cancer; Specimen; Survival Rate; Testing; Time; Translating; Validation; Variant; Women' s Health; X-Ray Computed Tomography; base; biomarker panel; candidate marker; cardiovascular health; case control; chemotherapy; clinical diagnosis; clinical practice; cohort; computed tomography screening; detection method; detection platform; early detection biomarkers; high dimensionality; implementation strategy; improved; lung cancer screening; lung small cell carcinoma; novel; screening; statistics; tumor

ABSTRACT/SUMMARY Small cell lung cancer (SCLC) is one of the few malignancies with such poor outcomes that it meets the definition of a “recalcitrant” cancer, accounting for 30,000 American lives each year with five-year survival rates of just ~7%. Somewhat lost in these dismal statistics is the fact that patients diagnosed early (limited stage) display vastly superior survival metrics when compared to those diagnosed late (extensive stage). Unfortunately, only a minority of cases are identified at limited stage, and the computed tomography (CT) screening approaches capable of early detection for non-small cell lung cancer (NSCLC) have not proven effective for SCLC. We will employ a novel two-mode, array based, hybrid plasma marker methodology capable of detecting autoantibody- autoantigen complex and unbound autoantibody markers for SCLC early detection. One of the major problems with studying SCLC is there are few studies and cohorts that have appropriate plasma samples. We have accumulated robust biomarker candidates centered around autoantibody-antigen complexes using the Cardiovascular Health Study (prediagnostic), Fred Hutch Lung Cancer Early Detection and Prevention Clinic, and Vanderbilt SCLC sample sets and will comprehensively define free autoantibodies levels in these same cohorts. We propose to test a fixed combination rule combining both autoantibody approaches using all of the prediagnostic SCLC samples from the Women's Health Initiative (WHI), the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO), and the National Lung Screening Trial (NLST) cohorts and diagnostic samples from Moffitt Cancer Center. Using prediagnostic samples allows us to effectively model early detection much more accurately than after diagnosis occurs, and this is particularly important for SCLC as diagnosis at the extensive stage is nearly almost always fatal. Part of our analysis will determine how early our autoantibody marker panel can predict the presence of SCLC and whether a tumor can be observed via CT at that time in order to evaluate the timing and implementation of our early-detection procedure.

摘要/总结 小细胞肺癌 (SCLC) 是少数几种预后极差且符合定义的恶性肿瘤之一 一种“顽固性”癌症，每年夺走 30,000 美国人的生命，五年生存率仅为 〜7％。在这些令人沮丧的统计数据中，有些人忽略了这样一个事实：早期（有限阶段）诊断的患者表现出 与晚期（广泛期）诊断的患者相比，生存指标要优越得多。不幸的是，只有一个 少数病例是在有限阶段发现的，并且计算机断层扫描 (CT) 筛查方法 能够早期检测非小细胞肺癌 (NSCLC)，但尚未证明对 SCLC 有效。我们将 采用新型两种模式、基于阵列的混合血浆标记方法，能够检测自身抗体- 用于 SCLC 早期检测的自身抗原复合物和未结合的自身抗体标记。主要问题之一 研究 SCLC 的一个问题是，很少有研究和队列拥有合适的血浆样本。我们有 使用以下方法积累了以自身抗体-抗原复合物为中心的强大的生物标志物候选物 心血管健康研究（诊断前），Fred Hutch 肺癌早期检测和预防诊所， 和范德比尔特 SCLC 样本集，并将全面定义这些样本中的游离自身抗体水平 队列。我们建议使用所有的方法来测试结合两种自身抗体方法的固定组合规则 来自妇女健康倡议 (WHI) 的前列腺、肺、结直肠、卵巢的诊断前 SCLC 样本 癌症筛查试验 (PLCO) 和国家肺部筛查试验 (NLST) 队列和诊断样本 来自莫菲特癌症中心。使用诊断前样本使我们能够有效地对早期检测进行建模 比诊断后更准确，这对于 SCLC 来说尤其重要，因为在诊断时就进行诊断 扩展阶段几乎总是致命的。我们分析的一部分将确定我们的自身抗体多久 标记物组合可以预测 SCLC 的存在以及当时是否可以通过 CT 观察到肿瘤 为了评估我们早期检测程序的时机和实施情况。