Zhang Jie, Zhu Changli, Gao Hong, Liang Xun, Fan Xiaoqian, Zheng Yulong, Chen Song, Wan Yufeng
Department of Respiratory Diseases, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China.
College of Nursing and Midwifery, Jiangsu College of Nursing, Huai'an, Jiangsu, China.
PeerJ. 2020 Dec 10;8:e10513. doi: 10.7717/peerj.10513. eCollection 2020.
We sought to identify the biomarkers related to the clinical severity of stage I to stage IV chronic obstructive pulmonary disease (COPD). Gene expression profiles from the blood samples of COPD patients at each of the four stages were acquired from the Gene Expression Omnibus Database (GEO, accession number: GSE54837). Genes showing expression changes among the different stages were sorted by soft clustering. We performed functional enrichment, protein-protein interaction (PPI), and miRNA regulatory network analyses for the differentially expressed genes. The biomarkers associated with the clinical classification of COPD were selected from logistic regression models and the relationships between TLR2 and inflammatory factors were verified in clinical blood samples by qPCR and ELISA. Gene clusters demonstrating continuously rising or falling changes in expression (clusters 1, 2, and 7 and clusters 5, 6, and 8, respectively) from stage I to IV were defined as upregulated and downregulated genes, respectively, and further analyzed. The upregulated genes were enriched in functions associated with defense, inflammatory, or immune responses. The downregulated genes were associated with lymphocyte activation and cell activation. TLR2, HMOX1, and CD79A were hub proteins in the integrated network of PPI and miRNA regulatory networks. TLR2 and CD79A were significantly correlated with clinical classifications. TLR2 was closely associated with inflammatory responses during COPD progression. Functions associated with inflammatory and immune responses as well as lymphocyte activation may play important roles in the progression of COPD from stage I to IV. and may serve as potential biomarkers for the clinical severity of COPD. and may also serve as independent biomarkers in the clinical classification in COPD. TLR2 may play an important role in the inflammatory responses of COPD.
我们试图确定与Ⅰ至Ⅳ期慢性阻塞性肺疾病（COPD）临床严重程度相关的生物标志物。从基因表达综合数据库（GEO，登录号：GSE54837）获取了四个阶段COPD患者血液样本的基因表达谱。通过软聚类对不同阶段表达发生变化的基因进行排序。我们对差异表达基因进行了功能富集、蛋白质-蛋白质相互作用（PPI）和miRNA调控网络分析。从逻辑回归模型中选择与COPD临床分类相关的生物标志物，并通过qPCR和ELISA在临床血液样本中验证TLR2与炎症因子之间的关系。从Ⅰ期到Ⅳ期表达呈持续上升或下降变化的基因簇（分别为簇1、2和7以及簇5、6和8）分别定义为上调基因和下调基因，并进一步分析。上调基因在与防御、炎症或免疫反应相关的功能中富集。下调基因与淋巴细胞活化和细胞活化相关。TLR2、HMOX1和CD79A是PPI和miRNA调控网络整合网络中的枢纽蛋白。TLR2和CD79A与临床分类显著相关。TLR2与COPD进展过程中的炎症反应密切相关。与炎症和免疫反应以及淋巴细胞活化相关的功能可能在COPD从Ⅰ期到Ⅳ期的进展中起重要作用。 和 可能作为COPD临床严重程度的潜在生物标志物。 和 也可能作为COPD临床分类中的独立生物标志物。TLR2可能在COPD的炎症反应中起重要作用。
