Gao Junyan, Wu Mingfu, Wang Fudong, Jiang Lijun, Tian Rui, Zhu Xueping, He Shan
Department of Pediatrics, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu.
Department of Pediatrics, The First People's Hospital of Kunming City, Kunming, Yunnan.
Medicine (Baltimore). 2020 Nov 25;99(48):e23477. doi: 10.1097/MD.0000000000023477.
Bronchopulmonary dysplasia (BPD) remains a major complication and accounts for high morbidity and mortality of preterm infants. The present study aimed to identify the key genes in the development of BPD and to provide some new insights into the pathogenesis of BPD. The GSE108754 dataset was downloaded from Gene Expression Omnibus database containing 5 samples of BPD patients and 6 of non-BPD infants. The differentially expressed genes (DEGs) between BPD and non-BPD patients were identified by R software. The pathway and function enrichment analyses were performed through Database for Annotation Visualization and Integrated Discovery website. The protein-protein interaction network for DEGs was established by Cytoscape software and the most highly connected module was selected through MCODE plugin. Furthermore, the clinical sample verification among 25 BPD patients and 10 non-BPD infants was carried out in our center. Finally, based on the results above, the gene set enrichment analysis focusing on CD74 upregulated status was employed. Totally, 189 DEGs including 147 upregulated genes and 42 downregulated genes between BPD and non-BPD patients were screened out. The pathway and function enrichments revealed these DEGs were mainly enriched in asthma, intestinal immune network for IgA production, antigen processing and presentation and immune response. Thirteen DEGs (CD74, HLA-DMA, HLA-DRA, HLA-DMB, HLA-DOB, HLA-DQA1, HLA-DRB5, HLA-DPA1, HLA-DOA, HLA-DPB1, HLA-DQB2, HLA-DQA2, and HLA-DQB1) were determined as hub genes. The mRNA expression levels of the 13 hub genes were tested by quantitative real-time polymerase chain reaction among our clinical samples. Eventually, CD74 was confirmed to be the most significant highly expressed in BPD samples (P < .001) and its expression level was negatively correlated with gestational age (r = -0.653) and birth weight (r = -0.675). The gene set enrichment analysis results showed the gene sets associated with lupus erythematosus, viral myocarditis, immune network for IgA production, graft versus host disease, cell adhesion molecules and so no were differentially enriched with the phenotype of high-expression CD74. In conclusion, CD74 may serve to predict the BPD development and provide a new therapeutic target for BPD.
支气管肺发育不良（BPD）仍然是一种主要并发症，是早产儿高发病率和高死亡率的原因。本研究旨在确定BPD发展过程中的关键基因，并为BPD的发病机制提供一些新见解。从基因表达综合数据库下载了GSE108754数据集，其中包含5例BPD患者样本和6例非BPD婴儿样本。通过R软件鉴定BPD患者和非BPD患者之间的差异表达基因（DEG）。通过注释、可视化和综合发现数据库网站进行通路和功能富集分析。通过Cytoscape软件建立DEG的蛋白质-蛋白质相互作用网络，并通过MCODE插件选择连接度最高的模块。此外，在我们中心对25例BPD患者和10例非BPD婴儿进行了临床样本验证。最后，基于上述结果，采用聚焦于CD74上调状态的基因集富集分析。共筛选出BPD患者和非BPD患者之间的189个DEG，其中包括上调基因147个，下调基因42个。通路和功能富集分析显示，这些DEG主要富集于哮喘、IgA产生的肠道免疫网络、抗原加工和呈递以及免疫反应。确定13个DEG（CD74、HLA-DMA、HLA-DRA、HLA-DMB、HLA-DOB、HLA-DQA1、HLA-DRB5、HLA-DPA1、HLA-DOA、HLA-DPB1、HLA-DQB2、HLA-DQA2和HLA-DQB1）为枢纽基因。通过定量实时聚合酶链反应检测了我们临床样本中13个枢纽基因的mRNA表达水平。最终，证实CD74在BPD样本中表达最高（P<0.001），其表达水平与胎龄（r=-0.653）和出生体重（r=-0.675）呈负相关。基因集富集分析结果显示，与红斑狼疮、病毒性心肌炎、IgA产生免疫网络、移植物抗宿主病、细胞黏附分子等相关的基因集在高表达CD74表型中差异富集。总之，CD74可能有助于预测BPD的发展，并为BPD提供新的治疗靶点。
