Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics
Selection of AECOPD-specific immunomodulatory biomarkers by integrating genomics and proteomics with clinical informatics
复制标题
将基因组学、蛋白质组学与临床信息学相结合，选择 AECOPD 特异性免疫调节生物标志物
DOI：
10.1007/s10565-017-9405-x
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发表时间：
2018-04-01
影响因子：
6.1
通讯作者：
Wang, Xiangdong
中科院分区：
文献类型：
--
作者：
Shi, Lin;Zhu, Bijun;Wang, Xiangdong
慢性阻塞性肺疾病急性加重（AECOPD）是一种严重的疾病，其死亡率和医疗费用都很高。全身炎症反应和免疫反应是影响AECOPD患者预后和质量的主要因素。在AECOPD特异性炎症生物标志物鉴定和验证的基础上，本研究旨在通过评估AECOPD患者入院后第1、3和10天外周血单个核细胞（PBMC）和血浆的动态基因组和蛋白质组学谱来鉴定AECOPD特异性免疫调节介质，并与健康对照或稳定期COPD患者进行比较。我们发现C1QC和C1RL的基因和蛋白在COPD或AECOPD患者中共差异上调表达，而触珠蛋白（HP）、ORM1、SERPING1和C3被鉴定为一组AECOPD特异性免疫调节介质。我们还发现炎症刺激可以通过PI3K信号通路上调A549细胞中骨桥蛋白（OPN）相关HP的表达。通过基因抑制阻断OPN的自分泌产生可以减少炎症诱导的肺上皮细胞的HP产生。AECOPD或COPD特异性免疫调节介质的复杂网络将有利于开发用于预防和治疗AECOPD的精确或个性化药物策略。
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) as a serious event has high mortality and medical costs. Systemic inflammation and immune response are the major factors influencing the outcome and quality of patient with AECOPD. On basis of identification and validation of AECOPD-specific inflammatory biomarkers, the present study aimed to identify AECOPD-specific immunomodulatory mediators by evaluating dynamic genomic and proteomic profiles of peripheral blood mononuclear cells (PBMCs) and plasma in patients with AECOPD on day 1, 3, and 10 after the hospital admission, to compare with healthy controls or patients with stable COPD. We found that genes and proteins of C1QC and C1RL were co-differentially up-expressed in patients with COPD or AECOPD, while haptoglobin (HP), ORM1, SERPING1, and C3 were identified as a panel of AECOPD-specific immunomodulatory mediators. We also found that inflammatory stimuli could up-regulate osteopontin (OPN)-associated HP expression through the PI3K signal pathway in A549 cells. Block of autocrine production of OPN by gene inhibition could reduce HP production from inflammation-induced lung epithelial cells. The complex network of AECOPD- or COPD-specific immunomodulatory mediators will benefit the development of precision or personalized medicine strategies for prevention and treatment of AECOPD.