Qi Quan, Yan Yibo, Luo Cheng, Fang Chen, Li Yugui, Cai Xiongwei, Ling Guoxing, Song Haitao, Zheng Baoshi
Department of Cardiac Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Heart Surg Forum. 2022 Mar 24;25(2):E243-E252. doi: 10.1532/hsf.4487.
Cardiopulmonary bypass (CPB), though indispensable in many cardiac surgery procedures, has several undesirable consequences. The aim of this study was to identify potential genes that may reduce the inflammatory response and complications after CPB. The GSE132176 dataset was selected from the Gene Expression Omnibus (GEO) database and included 10 patients with tetralogy of Fallot and 10 patients with an atrial septal defect who underwent CPB surgery. TSV files were downloaded after GEO2R processing. Protein-protein interaction analysis of common differentially expressed genes (DEGs) was performed using the Search Tool for the Retrieval of Interacting Genes. Gene modules and hub genes were visualized in the protein-protein interaction network using Cytoscape. Enrichment analysis was performed for all important DEGs, modular genes, and hub genes. A total of 72 DEGs were screened, including two functional and one hub gene module. FOS modular genes were primarily enriched in NGF-stimulated transcription, spinal cord injury, and PID AP1 pathway. The ATF3 modular gene was mainly enriched in cytomegalovirus infection and transcriptional misregulation in cancer. Hub gene modules were primarily enriched in the PID AP1 pathway, positive regulation of pri-miRNA transcription by RNA polymerase II, and the PID ATF2 pathway. FOS, JUN, ATF3, and EGR1 were the four most important hub genes; the top three hub genes were involved in the formation of AP-1 and enriched in the AP-1 pathway. Finally, we measured the expression levels of these four genes in patients undergoing CPB via qRT-PCR, and the results were consistent with those obtained in bioinformatic analysis. FOS, JUN, ATF3, and EGR1 and the AP-1 pathway may play key roles in inflammation and complications caused by CPB.
体外循环(CPB)虽然在许多心脏手术过程中不可或缺,但也有一些不良后果。本研究的目的是确定可能减少CPB后炎症反应和并发症的潜在基因。从基因表达综合数据库(GEO)中选择了GSE132176数据集,其中包括10例法洛四联症患者和10例接受CPB手术的房间隔缺损患者。经过GEO2R处理后下载了TSV文件。使用检索相互作用基因的搜索工具对常见差异表达基因(DEG)进行蛋白质-蛋白质相互作用分析。使用Cytoscape在蛋白质-蛋白质相互作用网络中可视化基因模块和枢纽基因。对所有重要的DEG、模块基因和枢纽基因进行富集分析。共筛选出72个DEG,包括两个功能基因模块和一个枢纽基因模块。FOS模块基因主要富集于NGF刺激的转录、脊髓损伤和PID AP1途径。ATF3模块基因主要富集于巨细胞病毒感染和癌症中的转录失调。枢纽基因模块主要富集于PID AP1途径、RNA聚合酶II对pri-miRNA转录的正调控以及PID ATF2途径。FOS、JUN、ATF3和EGR1是四个最重要的枢纽基因;前三个枢纽基因参与AP-1的形成并富集于AP-1途径。最后,我们通过qRT-PCR测量了接受CPB手术患者中这四个基因的表达水平,结果与生物信息学分析结果一致。FOS、JUN、ATF3、EGR1和AP-1途径可能在CPB引起的炎症和并发症中起关键作用。