Cai Jiayang, Ye Zhang, Hu Yuanyuan, Yang Ji'an, Wu Liquan, Yuan Fanen, Zhang Li, Chen Qianxue, Zhang Shenqi
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Front Cell Neurosci. 2022 Dec 19;16:1094500. doi: 10.3389/fncel.2022.1094500. eCollection 2022.
Ischemic stroke (IS) accounts for more than 80% of strokes and is one of the leading causes of death and disability in the world. Due to the narrow time window for treatment and the frequent occurrence of severe bleeding, patients benefit less from early intravenous thrombolytic drug therapy. Therefore, there is an urgent need to explore the molecular mechanisms poststroke to drive the development of new therapeutic approaches. Immunogenic cell death (ICD) is a type of regulatory cell death (RCD) that is sufficient to activate the adaptive immune response of immunocompetent hosts. Although there is growing evidence that ICD regulation of immune responses and immune responses plays an important role in the development of IS, the role of ICD in the pathogenesis of IS has rarely been explored. In this study, we systematically evaluated ICD-related genes in IS. The expression profiles of ICD-related genes in IS and normal control samples were systematically explored. We conducted consensus clustering, immune infiltration analysis, and functional enrichment analysis of IS samples using ICD differentially expressed genes. The results showed that IS patients could be classified into two clusters and that the immune infiltration profile was altered in different clusters. In addition, we performed machine learning to screen nine signature genes that can be used to predict the occurrence of disease. We also constructed nomogram models based on the nine risk genes (CASP1, CASP8, ENTPD1, FOXP3, HSP90AA1, IFNA1, IL1R1, MYD88, and NT5E) and explored the immune infiltration correlation, gene-miRNA, and gene-TF regulatory network of the nine risk genes. Our study may provide a valuable reference for further elucidation of the pathogenesis of IS and provide directions for drug screening, personalized therapy, and immunotherapy for IS.
缺血性中风(IS)占中风病例的80%以上,是全球死亡和残疾的主要原因之一。由于治疗时间窗狭窄且严重出血频繁发生,早期静脉溶栓药物治疗使患者受益较少。因此,迫切需要探索中风后的分子机制,以推动新治疗方法的开发。免疫原性细胞死亡(ICD)是一种调节性细胞死亡(RCD),足以激活免疫活性宿主的适应性免疫反应。尽管越来越多的证据表明ICD对免疫反应的调节在IS的发展中起重要作用,但ICD在IS发病机制中的作用很少被探索。在本研究中,我们系统地评估了IS中与ICD相关的基因。系统地探索了IS和正常对照样本中与ICD相关基因的表达谱。我们使用ICD差异表达基因对IS样本进行了一致性聚类、免疫浸润分析和功能富集分析。结果表明,IS患者可分为两个聚类,不同聚类中的免疫浸润谱发生了改变。此外,我们进行了机器学习以筛选出九个可用于预测疾病发生的特征基因。我们还基于九个风险基因(CASP1、CASP8、ENTPD1、FOXP3、HSP90AA1、IFNA1、IL1R1、MYD88和NT5E)构建了列线图模型,并探索了这九个风险基因的免疫浸润相关性、基因- miRNA和基因- TF调控网络。我们的研究可能为进一步阐明IS的发病机制提供有价值的参考,并为IS的药物筛选、个性化治疗和免疫治疗提供方向。