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）是为数不多的恶性肿瘤之一，其结果如此之差，以至于它符合定义 每年有3万美国人死于“恶性”癌症，五年生存率仅为 ~ 7%。在这些令人沮丧的统计数据中，有些人失去了这样一个事实，即早期诊断的患者（有限阶段）显示 与晚期诊断（广泛期）的患者相比，其生存指标大大优于上级患者。不幸的是，只有一个 少数病例在有限的阶段被确定，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）的药物尚未证明对SCLC有效。我们将 采用一种新的双模式、基于阵列的、能够检测自身抗体的混合血浆标志物方法， 自身抗原复合物和未结合的自身抗体标记物用于SCLC早期检测。的主要问题之一 在研究SCLC的过程中，很少有研究和队列具有适当的血浆样本。我们有 使用该方法，以自身抗体-抗原复合物为中心积累了稳健的生物标志物候选物。 心血管健康研究（诊断前），弗雷德哈奇肺癌早期检测和预防诊所， 和范德比尔特SCLC样本集，并将全面定义这些相同样本中的游离自身抗体水平。 同伙我们建议测试一个固定的组合规则，结合两种自身抗体的方法，使用所有的 来自妇女健康倡议（WHI）、前列腺、肺、结直肠、卵巢的诊断前SCLC样本 癌症筛查试验（PLCO）和国家肺筛查试验（NLST）队列和诊断样本 来自莫菲特癌症中心使用预诊断样本使我们能够有效地模拟早期检测， 更准确地比诊断发生后，这是特别重要的小细胞肺癌的诊断， 广泛期几乎总是致命的。我们的部分分析将确定我们的自身抗体 标记物组可以预测SCLC的存在以及肿瘤是否可以在那时通过CT观察到， 以评估我们的早期检测程序的时间和执行情况。