Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
EBioMedicine. 2020 Mar;53:102674. doi: 10.1016/j.ebiom.2020.102674. Epub 2020 Feb 26.
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.
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.
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.
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.
Research supported by grants from National Key Research and Development Program of China Grant (No. 2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813), Open Foundation of Key Laboratory of Systems Biomedicine (No. KLSB2017QN-01), Science and Technology Commission of Shanghai Municipality Medical Guidance Science &Technology Support Project (16411966100), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20172005), Shanghai Municipal Commission of Health and Family Planning Outstanding Academic Leaders Training Program (2017BR055) and National Natural Science Foundation of China (81871882).
针对肿瘤相关抗原的自身抗体与癌症进展高度相关。自身抗体可以作为肿瘤负担的指标，并有可能监测治疗反应和肿瘤复发。然而，针对癌症治疗，自身抗体库如何变化在很大程度上尚不清楚。
连续采集五例肺腺癌患者手术前后的血清。将这些血清在包含 20240 个重组蛋白的人类蛋白质组微阵列上进行分析，以获得针对手术的动态自身抗体库，并鉴定肿瘤切除或手术后抗体反应降低的抗原，称为手术相关抗原。然后，使用该鉴定出的候选抗原构建聚焦微阵列，并使用同一位患者的多个时间点的纵向采集的血清以及 45 例肺腺癌患者的更大队列进行验证。
患者之间的自身抗体谱高度可变。同时，同一位患者的血清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 6 种手术相关抗原。所有 5 例患者均至少有一种手术相关抗原，表明这种类型的生物标志物普遍存在，而个体之间特定抗原的共享性很差。根据对更大队列的测试，每种抗原的患病率为 2%-14%。
据我们所知，这是第一项针对癌症患者手术前后自身抗体库进行动态分析的研究。手术相关抗原的高患病率意味着在人群中监测肿瘤复发具有广泛的应用潜力，而特定抗原的低患病率允许进行个性化治疗。在积累和分析更多的纵向样本后，将手术相关的血清生物标志物组合成一个面板，可用于个性化地发出肿瘤复发警报。
本研究由国家重点研发计划（No. 2016YFA0500600）、国家自然科学基金（No. 31970130、31600672、31670831、31370813）、系统生物医学重点实验室开放基金（No. KLSB2017QN-01）、上海市科委医学引导类科技支撑项目（16411966100）、上海市教委高峰高原学科建设计划（20172005）、上海市卫生和计划生育委员会优秀学科带头人培养计划（2017BR055）和国家自然科学基金（81871882）资助。
