CD19 and POU2AF1 are Potential Immune-Related Biomarkers Involved in the Emphysema of COPD: On Multiple Microarray Analysis.
CD19 and POU2AF1 are Potential Immune-Related Biomarkers Involved in the Emphysema of COPD: On Multiple Microarray Analysis.
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CD19 和 POU2AF1 是参与 COPD 肺气肿的潜在免疫相关生物标志物：多重微阵列分析
DOI：
10.2147/jir.s355764
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发表时间：
2022
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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目的肺气肿是慢性阻塞性肺疾病(COPD)进展的主要原因。本研究旨在寻找与COPD相关肺气肿相关的关键基因。患者和方法GSE76925从基因表达总览数据库下载。构建了对照组和COPD组之间差异表达基因的蛋白质-蛋白质相互作用网络，以利用Cytoscape鉴定HUB基因。使用接收器工作特性分析来评估HUB基因的诊断性能。通过分析HUB基因与肺气肿的肺功能和CT指标的关系，进行相关分析以确定关键基因。然后根据关键基因表达的中位数将COPD患者分为两组，并确定这两组之间的DEG。并对DEGS的富集分析和关键基因与免疫细胞渗透的相关性进行了分析。最后，在肺组织数据集(GSE47460)和血液数据集(GSE76705)中评估了关键基因的作用。用实时定量聚合酶链式反应和免疫组织化学方法验证关键基因的表达。结果CD19、POU2AF1对COPD有诊断价值，且与肺功能、肺气肿CT指标显著相关。CD19和POU2AF1与慢性阻塞性肺疾病的B细胞相关。这些结果在GSE47460中是一致的。CD19和POU2AF1在血液中的表达与肺组织中的表达相反，CD19和POU2AF1在COPD肺组织中的表达在mRNA和蛋白水平均显著上调。结论CD19和POU2AF1可能是肺气肿的关键调节因子，并可能通过调节B细胞免疫功能参与COPD的进展。靶向B细胞可能是治疗COPD的一种有前途的策略。
Purpose Emphysema is the main cause of the progression of chronic obstructive pulmonary disease (COPD). This study aimed to identify the key genes involved in COPD-related emphysema. Patients and Methods GSE76925 was downloaded from Gene Expression Omnibus database. Protein–protein interaction networks of differentially expressed genes (DEGs) between control and COPD groups were constructed to identify hub genes using Cytoscape. Diagnostic performance of hub genes was evaluated using receiver operating characteristic analysis. Correlation analysis was performed to identify the key genes by analyzing the relationship between the hub genes and lung function and computed tomography (CT) indexes of emphysema. COPD patients were then divided into two groups based on the median expression of key genes and DEGs between these two groups were identified. Enrichment analysis of DEGs and correlation analysis between key genes and the infiltration of the immune cells were also analyzed. Finally, the role of key genes was evaluated in a lung tissues dataset (GSE47460) and a blood dataset (GSE76705). Additionally, the expression of key genes was validated by quantitative real-time polymerase chain reaction and immunohistochemistry. Results CD19 and POU2AF1 had diagnostic efficacy for COPD and were significantly correlated with lung function and CT indexes of emphysema. Enrichment and immune analyses revealed that CD19 and POU2AF1 were correlated with the B cells in COPD. These results were consistent in GSE47460. The expression of CD19 and POU2AF1 in blood was the opposite of that in lung tissues, and CD19 and POU2AF1 were both significantly upregulated in COPD lung tissues at both the mRNA and protein levels. Conclusion CD19 and POU2AF1 may serve as key regulators of emphysema and contribute to the progression of COPD by regulating the B-cell immunology. Targeting B cells may be a promising strategy for treating COPD.