背景:急性心肌损伤,细胞因子风暴,低氧血症和病原体介导的损伤是2019年冠状病毒病(COVID-19)相关性心肌炎导致死亡的主要原因。这些需要ECMO治疗。我们调查了COVID-19相关心肌炎患者的差异表达基因(DEGs)和ECMO预后。
方法:分析GSE150392和GSE93101以鉴定DEGs。使用维恩图获得心肌炎相关和ECMO相关的DEGs之间的相同转录本。进行富集途径分析并鉴定hub基因。关键miRNA,转录因子,并鉴定了具有筛选基因相互作用的化学物质。GSE167028数据集和单细胞测序数据用于验证筛选的基因。
结果:使用维恩图,在心肌炎相关和ECMO相关的DEG之间确定了229个重叠的DEG,主要参与T细胞活化,收缩肌动蛋白丝束,肌动球蛋白,环核苷酸磷酸二酯酶活性,和细胞因子-细胞因子受体相互作用。筛选了15个hub基因和15个相邻的DEG,主要参与T细胞活化的正向调节,整合素复合物,整合素结合,PI3K-Akt信号通路,和TNF信号通路。GSE167028中的数据和单细胞测序数据用于验证筛选的基因,这表明筛选的基因CCL2,APOE,ITGB8、LAMC2、COL6A3和TNC主要在成纤维细胞中表达;IL6、ITGA1、PTK2、ITGB5、IL15、LAMA4、CAV1、SNCA、BDNF,ACTA2、CD70、MYL9、DPP4、ENO2和VEGFC在心肌细胞中表达;IL6、PTK2、ITGB5、IL15、APOE、JUN,SNCA,CD83、DPP4和ENO2在巨噬细胞中表达;IL6、ITGA1、PTK2、ITGB5、IL15、VCAM1、LAMA4、CAV1、ACTA2、MYL9、CD83、DPP4、ENO2、VEGFC和IL32在血管内皮细胞中表达。
结论:筛选的hub基因,IL6,ITGA1,PTK2,ITGB3,ITGB5,CCL2,IL15,VCAM1,GZMB,APOE,ITGB8,LAMA4,LAMC2,COL6A3和TNFRSF9,使用GEO数据集和单细胞测序数据进行验证,这可能是治疗目标的心肌炎患者,以防止MI进展和不良心血管事件。
BACKGROUND: Acute myocardial injury, cytokine storms, hypoxemia and pathogen-mediated damage were the major causes responsible for mortality induced by coronavirus disease 2019 (COVID-19)-related myocarditis. These need ECMO treatment. We investigated differentially expressed genes (DEGs) in patients with COVID-19-related myocarditis and ECMO prognosis.
METHODS: GSE150392 and GSE93101 were analyzed to identify DEGs. A Venn diagram was used to obtain the same transcripts between myocarditis-related and ECMO-related DEGs. Enrichment pathway analysis was performed and hub genes were identified. Pivotal miRNAs, transcription factors, and chemicals with the screened gene interactions were identified. The GSE167028 dataset and single-cell sequencing data were used to validate the screened genes.
RESULTS: Using a Venn diagram, 229 overlapping DEGs were identified between myocarditis-related and ECMO-related DEGs, which were mainly involved in T cell activation, contractile actin filament bundle, actomyosin, cyclic nucleotide phosphodiesterase activity, and cytokine-cytokine receptor interaction. 15 hub genes and 15 neighboring DEGs were screened, which were mainly involved in the positive regulation of T cell activation, integrin complex, integrin binding, the PI3K-Akt signaling pathway, and the TNF signaling pathway. Data in GSE167028 and single-cell sequencing data were used to validate the screened genes, and this demonstrated that the screened genes CCL2, APOE, ITGB8, LAMC2, COL6A3 and TNC were mainly expressed in fibroblast cells; IL6, ITGA1, PTK2, ITGB5, IL15, LAMA4, CAV1, SNCA, BDNF, ACTA2, CD70, MYL9, DPP4, ENO2 and VEGFC were expressed in cardiomyocytes; IL6, PTK2, ITGB5, IL15, APOE, JUN, SNCA, CD83, DPP4 and ENO2 were expressed in macrophages; and IL6, ITGA1, PTK2, ITGB5, IL15, VCAM1, LAMA4, CAV1, ACTA2, MYL9, CD83, DPP4, ENO2, VEGFC and IL32 were expressed in vascular endothelial cells.
CONCLUSIONS: The screened hub genes, IL6, ITGA1, PTK2, ITGB3, ITGB5, CCL2, IL15, VCAM1, GZMB, APOE, ITGB8, LAMA4, LAMC2, COL6A3 and TNFRSF9, were validated using GEO dataset and single-cell sequencing data, which may be therapeutic targets patients with myocarditis to prevent MI progression and adverse cardiovascular events.