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/摘要 小细胞肺癌（SCLC）是为数不多的症状，符合定义的恶性肿瘤之一 “顽固性”癌症的癌症，每年有30,000人的生活，五年生存率仅为 〜7％。在这些令人沮丧的统计数据中有些损失的事实是，患者早期诊断出（有限阶段）显示 与被诊断晚期（广泛的阶段）相比，生存指标非常出色。不幸的是，只有一个 在有限阶段确定了少数病例，计算机断层扫描（CT）筛选方法 能够早期检测非小细胞肺癌（NSCLC）尚未证明对SCLC有效。我们将 员工一种新型的两种模式，基于阵列的杂化等离子体标记方法，能够检测自身抗体 - 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 随着SCLC的研究，很少有适当的血浆样品的研究和同类群。我们有 累积的强大生物标志物候选者使用该候选物 心血管健康研究（诊断性诊断），弗雷德哈奇肺癌早期检测和预防诊所， 和Vanderbilt SCLC样本集，并将全面定义自动抗体级别 同伙。我们建议使用所有的所有自身抗体方法测试固定组合规则 妇女健康计划（WHI），前列腺，肺，结直肠，卵巢的诊断性SCLC样品 癌症筛查试验（PLCO）和国家肺筛查试验（NLST）和诊断样品 来自莫菲特癌症中心。使用诊断样品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作为诊断尤其重要 广泛的阶段几乎总是致命的。我们的一部分分析将确定我们的自身抗体的早期 标记面板可以预测SCLC的存在以及当时是否可以通过CT观察到肿瘤 为了评估我们的早期检测程序的时间和实施。