Tumor-specific autoantibodies for SCLC early detection

摘要/摘要 小细胞肺癌(SCLC)是少数几种预后如此差的恶性肿瘤之一，它符合定义 一种顽固性癌症，每年导致3万美国人死亡，五年存活率仅为 ~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，即早期(有限阶段)诊断的患者表现出 与诊断为晚期(广泛阶段)的患者相比，生存指标要优越得多。不幸的是，只有 少数病例是在有限的阶段确定的，计算机体层摄影(CT)筛查方法 能够早期发现非小细胞肺癌(NSCLC)的药物尚未被证明对小细胞肺癌有效。我们会 采用一种新的双模式、基于阵列的混合血浆标记物方法，能够检测自身抗体- 自身抗原复合体和游离自身抗体标记物用于小细胞肺癌早期检测。其中一个主要问题是 随着对小细胞肺癌的研究，很少有研究和队列有合适的血浆样本。我们有 累积的以自身抗体-抗原复合体为中心的稳健生物标志物候选者使用 心血管健康研究(诊断前)，弗雷德·哈奇肺癌早期发现和预防诊所， 和Vanderbilt 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 一群人。我们建议测试一种结合两种自身抗体方法的固定组合规则，使用所有 诊断前小细胞肺癌样本来自妇女健康倡议(WHI)、前列腺、肺、结直肠、卵巢 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模拟早期检测 比诊断后更准确，这对小细胞肺癌尤其重要，因为在 广泛的阶段几乎总是致命的。我们的部分分析将确定我们的自身抗体多早 标记物面板可以预测小细胞肺癌的存在以及当时是否可以通过CT观察到肿瘤 以评估我们早期发现程序的时机和实施情况。

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.