Longitudinal serum autoantibody repertoire profiling identifies surgery-associated biomarkers in lung adenocarcinoma

Longitudinal serum autoantibody repertoire profiling identifies surgery-associated biomarkers in lung adenocarcinoma
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纵向血清自身抗体库分析可识别肺腺癌中手术相关的生物标志物

DOI:
10.1016/j.ebiom.2020.102674
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发表时间:
2020-03-01
期刊:
影响因子:
11.1
通讯作者:
Tao, Sheng-ce
Tao, Sheng-ce
中科院分区:
医学1区
文献类型:
--
作者:
Li, Yang;Li, Cheng-qiang;Tao, Sheng-ce

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背景:抗肿瘤相关抗原的自身抗体与肿瘤进展高度相关。自身抗体可作为肿瘤负荷的指标,并有可能监测治疗反应和肿瘤复发。然而,如何自身抗体库的变化,以应对癌症treatment.Methods:血清5例肺腺癌患者手术前后,纵向收集。在20,240个重组蛋白的人蛋白质组微阵列上分析这些血清,以获得响应于手术的动态自身抗体库,以及鉴定肿瘤切除或手术后抗体应答降低的抗原,称为手术相关抗原。确定的候选抗原,然后被用来构建聚焦微阵列和验证纵向血清收集从不同的时间点的同一个病人和一个更大的队列的45个血清从肺腺癌patients.Findings:的自身抗体的档案是高度可变的患者之间。同时,来自同一患者的血清的自身抗体谱在手术后至少3个月内惊人地稳定。鉴定并验证了六种手术相关抗原。所有五名患者都至少有一种手术相关抗原,表明这种类型的生物标志物是普遍的,而特异性抗原在个体之间的共享性很差。每种抗原的患病率为2%-14%.Interpretation根据测试与一个更大的队列:据我们所知,这是第一个研究动态分析的自身抗体库前/后手术的癌症患者。手术相关抗原的高流行率意味着可能广泛应用于监测人群中的肿瘤复发,而特异性抗原的低流行率允许个性化用药。在积累和分析更多纵向样本之后,手术相关血清生物标志物组合为一组,可以以个性化方式应用于警报肿瘤的复发。(c)2020年,任作家。由Elsevier B. V.出版,这是CC BY-NC-ND许可下的开放获取文章。(http://creativecommons.org/licenses/by-nc-nd/4.0/)
Background: Autoantibodies against tumor associated antigens are highly related to cancer progression. Autoantibodies could serve as indicators of tumor burden, and have the potential to monitor the response of treatment and tumor recurrence. However, how the autoantibody repertoire changes in response to cancer treatment are largely unknown.Methods: Sera of five lung adenocarcinoma patients before and after surgery, were collected longitudinally. These sera were analyzed on a human proteome microarray of 20,240 recombinant proteins to acquire dynamic autoantibody repertoire in response to surgery, as well as to identify the antigens with decreased antibody response after tumor excision or surgery, named as surgery-associated antigens. The identified candidate antigens were then used to construct focused microarray and validated by longitudinal sera collected from a variety of time points of the same patient and a larger cohort of 45 sera from lung adenocarcinoma patients.Findings: The autoantibody profiles are highly variable among patients. Meanwhile, the autoantibody profiles of the sera from the same patient were surprisingly stable for at least 3 months after surgery. Six surgery-associated antigens were identified and validated. All the five patients have at least one surgery-associated antigen, demonstrating this type of biomarkers is prevalent, while specific antigens are poorly shared among individuals. The prevalence of each antigen is 2%-14% according to the test with a larger cohort.Interpretation: To our knowledge, this is the first study of dynamically profiling of autoantibody repertoires before/after surgery of cancer patients. The high prevalence of surgery-associated antigens implies the possible broad application for monitoring of tumor recurrence in population, while the low prevalence of specific antigens allows personalized medicine. After the accumulation and analysis of more longitudinal samples, the surgery-associated serum biomarkers, combined as a panel, may be applied to alarm the recurrence of tumor in a personalized manner. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/)