Occurrence of Autoantibodies to Annexin I, 14-3-3 Theta and LAMR1 in Prediagnostic Lung Cancer Sera
Occurrence of Autoantibodies to Annexin I, 14-3-3 Theta and LAMR1 in Prediagnostic Lung Cancer Sera
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DOI：
10.1200/jco.2008.16.2388
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发表时间：
2008-11-01
影响因子：
45.3
通讯作者：
Hanash, Samir M.
中科院分区：
文献类型：
--
作者：
Qiu, Ji;Choi, Gina;Hanash, Samir M.
目的 我们已经实现了一个用于定量分析血清自身抗体的高通量平台，我们已将其应用于肺癌，以发现新的抗原，并在诊断前血清中验证针对诊断前收集的血清分析所定义的抗原的自身抗体。 材料和方法对来自人肺腺癌细胞系 A549 裂解物的蛋白质进行广泛的分级分离。将所得 1,824 个级分一式两份地点在硝化纤维包被的载玻片上。产生的微阵列用于盲法验证研究，以确定先前发现的新诊断肺癌患者自身抗体靶标的膜联蛋白 I、PGP9.5 和 14-3-3 theta 抗原是否与症状前阶段收集的血清中的自身抗体相关，并确定是否可以在诊断前血清中鉴定出其他抗原。肺癌诊断前 1 年内收集的 85 名患者的个体血清和来自胡萝卜素和视黄醇功效试验 (CARET) 队列的 85 名匹配对照者的个体血清与个体微阵列杂交。结果我们提供了肺癌血清中出现膜联蛋白 I、14-3-3 θ 自身抗体和一种新型肺癌抗原 LAMR1 的证据，这些抗体出现在症状出现和诊断之前。一种在症状出现之前诊断肺癌的方法，包括筛查针对特定抗原的自身抗体。临床肿瘤杂志 26：5060-5066。 (C) 2008 年美国临床肿瘤学会
Purpose We have implemented a high throughput platform for quantitative analysis of serum autoantibodies, which we have applied to lung cancer for discovery of novel antigens and for validation in prediagnostic sera of autoantibodies to antigens previously defined based on analysis of sera collected at the time of diagnosis.Materials and Methods Proteins from human lung adenocarcinoma cell line A549 lysates were subjected to extensive fractionation. The resulting 1,824 fractions were spotted in duplicate on nitrocellulose-coated slides. The microarrays produced were used in a blinded validation study to determine whether annexin I, PGP9.5, and 14-3-3 theta antigens previously found to be targets of autoantibodies in newly diagnosed patients with lung cancer are associated with autoantibodies in sera collected at the presymptomatic stage and to determine whether additional antigens may be identified in prediagnostic sera. Individual sera collected from 85 patients within 1 year before a diagnosis of lung cancer and 85 matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were hybridized to individual microarrays.Results We present evidence for the occurrence in lung cancer sera of autoantibodies to annexin I, 14-3-3 theta, and a novel lung cancer antigen, LAMR1, which precede onset of symptoms and diagnosis.Conclusion Our findings suggest potential utility of an approach to diagnosis of lung cancer before onset of symptoms that includes screening for autoantibodies to defined antigens. J Clin Oncol 26: 5060-5066. (C) 2008 by American Society of Clinical Oncology