Human Antibody Lab, Innovation Center, Pasteur Institute of Iran, Tehran, Iran.
Department of Microbial Biotechnology, Islamic Azad University, Pharmaceutical Sciences Branch, Tehran, Iran.
Sci Rep. 2017 Oct 23;7(1):13812. doi: 10.1038/s41598-017-14195-1.
Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.
吸烟是全球范围内导致肺癌的主要原因。在这项研究中,我们评估了非小细胞肺癌(NSCLC)患者和吸烟者(SM)的血清自身抗体(AAb)谱,从而确定了与 NSCLC 发病机制相关的过度激活途径和枢纽。我们对来自 NSCLC 组和 SM 组血清中的 IgG 进行了表面和溶液相生物淘选。总共检测到 20 个 NSCLC 特异性肽和 12 个 SM 特异性肽,这些肽被用于生成 NSCLC 和 SM 蛋白数据集。使用 STRING 和 Gephi 可视化 NSCLC 和 SM 相关蛋白,并使用 Enrichr 分析它们的模块。通过整合过度表达的途径,如癌症途径、表皮生长因子受体、c-Met、白细胞介素-4(IL-4)和 IL-6 信号通路,以及一组蛋白质(如磷脂酶 D(PLD)、IL-4 受体、IL-17 受体、层粘连蛋白、胶原蛋白和粘蛋白)到 PLD 途径和炎症细胞因子网络中,作为两组中最重要的事件,构建了两个超级网络,以阐明 NSCLC 发病机制的新方面,并确定吸烟对肿瘤形成的影响。总之,使用系统生物学方法评估 AAb 谱可以描绘各种疾病中涉及的隐藏事件。