An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer
An immune response manifested by the common occurrence of annexins I and II autoantibodies and high circulating levels of IL-6 in lung cancer
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DOI：
10.1073/pnas.171320598
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发表时间：
2001-08-14
影响因子：
11.1
通讯作者：
Hanash, SM
中科院分区：
文献类型：
--
作者：
Brichory, FM;Misek, DE;Hanash, SM
循环肿瘤抗原或其相关自身抗体的鉴定提供了早期癌症诊断的手段以及治疗的线索。本研究的目的是通过使用蛋白质组学方法鉴定通常诱导肺癌体液应答的蛋白质，并研究可能与自身抗体发展相关的生物学过程。将来自肺腺癌细胞系（A549）和肺肿瘤的溶解蛋白的等分试样进行二维PAGE，然后进行Western印迹分析，其中测试个体血清的一抗。分析了54例新诊断肺癌患者和60例其他癌症患者以及61例非癌症对照的血清。60%的肺腺癌患者和33%的肺鳞状细胞癌患者的血清，但没有一个非癌症对照组表现出IgG为基础的反应性，对蛋白质鉴定为糖基化膜联蛋白I和/或II。免疫组化分析显示，膜联蛋白I在肺肿瘤组织中的肿瘤细胞中弥漫表达，而膜联蛋白II主要在细胞表面表达。有趣的是，与抗体阴性患者和对照组相比，抗体阳性肺癌患者血清中的IL-6水平显著更高。我们的结论是，免疫反应所表现的膜联蛋白I和II自身抗体通常发生在肺癌，并与高循环水平的炎性细胞因子。我们已经实施的蛋白质组学方法具有实用性的发展，基于血清的检测癌症诊断，因为我们在本文中报告的发现antiannexins I和/或II在肺癌患者的血清中。
The identification of circulating tumor antigens or their related autoantibodies provides a means for early cancer diagnosis as well as leads for therapy. The purpose of this study was to identify proteins that commonly induce a humoral response in lung cancer by using a proteomic approach and to investigate biological processes that may be associated with the development of autoantibodies. Aliquots of solubilized proteins from a lung adenocarcinoma cell line (A549) and from lung tumors were subjected to two-dimensional PAGE, followed by Western blot analysis in which individual sera were tested for primary antibodies. Sera from 54 newly diagnosed patients with lung cancer and 60 patients with other cancers and from 61 noncancer controls were analyzed. Sera from 60% of patients with lung adenocarcinoma and 33% of patients with squamous cell lung carcinoma but none of the noncancer controls exhibited IgG-based reactivity against proteins identified as glycosylated annexins I and/or II. Immunohistochemical analysis showed that annexin I was expressed diffusely in neoplastic cells in lung tumor tissues, whereas annexin II was predominant at the cell surface. Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls. We conclude that an immune response manifested by annexins I and II autoantibodies occurs commonly in lung cancer and is associated with high circulating levels of an inflammatory cytokine. The proteomic approach we have implemented has utility for the development of serum-based assays for cancer diagnosis as we report in this paper on the discovery of antiannexins I and/or II in sera from patients with lung cancer.