Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer
Whole Genome-Derived Tiled Peptide Arrays Detect Prediagnostic Autoantibody Signatures in Non-Small-Cell Lung Cancer
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DOI：
10.1158/0008-5472.can-18-1536
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发表时间：
2019-04-01
期刊：
影响因子：
11.2
通讯作者：
Hanash, Samir M.
中科院分区：
文献类型：
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作者：
Yan, Yuanqing;Sun, Nan;Hanash, Samir M.
大多数非小细胞肺癌（NSCLC）病例在晚期被诊断出来，主要是因为疾病的早期阶段要么无症状，要么可能归因于其他原因，例如感染或吸烟的长期影响。因此，早期发现 NSCLC 可能会因及时干预而提高缓解率和生存率。在这里，我们利用一种基于全基因组衍生平铺肽阵列的新方法来识别与 NSCLC 中自身抗体反应性相关的表位，作为早期检测的潜在手段。阵列由 2,781,902 个平铺肽组成，代表人类基因组中编码的 20,193 个蛋白质。对来自高风险队列的 86 个诊断前样本和 86 个匹配的正常对照的分析显示，与对照相比，NSCLC 样本中有 48 种具有三个或更多反应性表位的蛋白质。独立质谱分析鉴定出 NSCLC 样本诊断前血清中 48 种蛋白质中的 40 种，其中 21 种出现在免疫球蛋白结合部分中。此外，63 和 34 个蛋白质分别包含三个或多个对于鳞状细胞肺癌和肺腺癌不同的表位。总的来说，这些数据表明平铺肽阵列提供了一种描绘基因组中编码的表位的方法，这些表位触发与肿瘤发展相关的自身抗体反应。意义：这项研究为精准肿瘤学的非小细胞肺癌早期诊断提供了一种模式，可应用于其他癌症类型。
The majority of non-small-cell lung cancer (NSCLC) cases are diagnosed at advanced stages, primarily because earlier stages of the disease are either asymptomatic or may be attributed to other causes such as infection or long-term effects from smoking. Therefore, early detection of NSCLC would likely increase response and survival rates due to timely intervention. Here, we utilize a novel approach based on whole genome-derived tiled peptide arrays to identify epitopes associated with autoantibody reactivity in NSCLC as a potential means for early detection. Arrays consisted of 2,781,902 tiled peptides representing 20,193 proteins encoded in the human genome. Analysis of 86 prediagnostic samples and 86 matched normal controls from a high-risk cohort revealed 48 proteins with three or more reactive epitopes in NSCLC samples relative to controls. Independent mass spectrometry analysis identified 40 of the 48 proteins in prediagnostic sera from NSCLC samples, of which, 21 occurred in the immunoglobulin-bound fraction. In addition, 63 and 34 proteins encompassed three or more epitopes that were distinct for squamous cell lung cancer and lung adenocarcinoma, respectively. Collectively, these data show that tiled peptide arrays provide a means to delineate epitopes encoded across the genome that trigger an autoantibody response associated with tumor development.Significance: This study provides a modality for early diagnosis of NSCLC for precision oncology that can be applied to other cancer types.