使用生物信息学分析鉴定与心力衰竭氧化应激相关的枢纽基因及其与免疫浸润的相关性。
Identification of hub genes associated with oxidative stress in heart failure and their correlation with immune infiltration using bioinformatics analysis.
机构信息
Department of Cardiology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
Department of Cardiology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China.
出版信息
PeerJ. 2023 Aug 18;11:e15893. doi: 10.7717/peerj.15893. eCollection 2023.
Both oxidative stress and the immune response are associated with heart failure (HF). In this study, our aim was to identify the hub genes associated with oxidative stress andimmune infiltration of HF by bioinformatics analysis and experimental verification. The expression profile of GSE36074 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened by GEO2R. The genes related to oxidative stress were extracted from GeneCards websites. Then, the functional enrichment analysis of oxidative stress-related DEGs (OSRDEGs) was performed using DAVID. In addition, we constructed a protein-protein interaction (PPI) network using the STRING database and screened for hub genes with Cytoscape software. We also used CIBERSORTx to analyze immune infiltration in mice heart tissues between the TAC and Sham groups and explored the correlation between immune cells and hub genes. Finally, the hub genes were carried out using reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and western blot. A total of 136 OSRDEGs were found in GSE36074. Enrichment analysis revealed that these OSRDEGs were enriched in the mitochondrion, HIF-1, FoxO, MAPK and TNF signaling pathway. The five hub genes (Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1) were screened by the cytoHubba plugin. The correlation analysis between immune cells and hub genes showed that Mapk14 was positively correlated with Th2 Cells, while Hif1a and Hsp90ab1exhibited a negative correlation with Th2 Cells; Myc exhibited a negative correlation with Monocytes; whereas, Hsp90aa1 was negatively correlated with NK Resting. Finally, five hub genes were validated by RT-qPCR, IHC and western blot. Mapk14, Hif1a, Myc, Hsp90ab1, and Hsp90aa1 are hub genes of HF and may play a critical role in the oxidative stress of HF. This study may provide new targets for the treatment of HF, and the potential immunotherapies are worthy of further study.
氧化应激和免疫反应都与心力衰竭（HF）有关。在这项研究中，我们的目的是通过生物信息学分析和实验验证来鉴定与 HF 的氧化应激和免疫浸润相关的枢纽基因。从基因表达综合（GEO）数据库中获得 GSE36074 的表达谱。使用 GEO2R 筛选差异表达基因（DEGs）。从 GeneCards 网站提取与氧化应激相关的基因。然后，使用 DAVID 对氧化应激相关 DEGs（OSRDEGs）进行功能富集分析。此外，我们使用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络，并使用 Cytoscape 软件筛选枢纽基因。我们还使用 CIBERSORTx 分析 TAC 和 Sham 组小鼠心脏组织中的免疫浸润，并探索免疫细胞与枢纽基因之间的相关性。最后，使用逆转录定量 PCR（RT-qPCR）、免疫组织化学（IHC）和 Western blot 对枢纽基因进行验证。在 GSE36074 中发现了 136 个 OSRDEGs。富集分析表明，这些 OSRDEGs 富集在线粒体、HIF-1、FoxO、MAPK 和 TNF 信号通路中。通过 cytoHubba 插件筛选出五个枢纽基因（Mapk14、Hif1a、Myc、Hsp90ab1 和 Hsp90aa1）。枢纽基因与免疫细胞的相关性分析表明，Mapk14 与 Th2 细胞呈正相关，而 Hif1a 和 Hsp90ab1 与 Th2 细胞呈负相关；Myc 与单核细胞呈负相关；而 Hsp90aa1 与 NK 静息细胞呈负相关。最后，通过 RT-qPCR、IHC 和 Western blot 验证了五个枢纽基因。Mapk14、Hif1a、Myc、Hsp90ab1 和 Hsp90aa1 是 HF 的枢纽基因，可能在 HF 的氧化应激中发挥关键作用。这项研究可能为 HF 的治疗提供新的靶点，潜在的免疫疗法值得进一步研究。
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