Sun Kaiwen, Li Hongwei, Dong Yang, Cao Lei, Li Dongpeng, Li Jinghong, Zhang Manxia, Yan Dongming, Yang Bo
The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China.
Mol Neurobiol. 2025 Mar;62(3):3098-3124. doi: 10.1007/s12035-024-04433-9. Epub 2024 Sep 4.
Cerebral ischemia‒reperfusion injury (CIRI) is a type of secondary brain damage caused by reperfusion after ischemic stroke due to vascular obstruction. In this study, a CIRI diagnostic model was established by identifying hypoxia-related differentially expressed genes (HRDEGs) in patients with CIRI. The ischemia‒reperfusion injury (IRI)-related datasets were downloaded from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ), and hypoxia-related genes in the Gene Cards database were identified. After the datasets were combined, hypoxia-related differentially expressed genes (HRDEGs) expressed in CIRI patients were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the HRDEGs were performed using online tools. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed with the combined gene dataset. CIRI diagnostic models based on HRDEGs were constructed via least absolute shrinkage and selection operator (LASSO) regression analysis and a support vector machine (SVM) algorithm. The efficacy of the 9 identified hub genes for CIRI diagnosis was evaluated via mRNA‒microRNA (miRNA) interaction, mRNA-RNA-binding protein (RBP) network interaction, immune cell infiltration, and receiver operating characteristic (ROC) curve analyses. We then performed logistic regression analysis and constructed logistic regression models based on the expression of the 9 HRDEGs. We next established a nomogram and calibrated the prediction data. Finally, the clinical utility of the constructed logistic regression model was evaluated via decision curve analysis (DCA). This study revealed 9 critical genes with high diagnostic value, offering new insights into the diagnosis and selection of therapeutic targets for patients with CIRI. : Not applicable.
脑缺血再灌注损伤(CIRI)是由于血管阻塞导致缺血性中风后再灌注引起的一种继发性脑损伤。在本研究中,通过鉴定CIRI患者中与缺氧相关的差异表达基因(HRDEGs)建立了CIRI诊断模型。从基因表达综合数据库(GEO)数据库(http://www.ncbi.nlm.nih.gov/geo)下载缺血再灌注损伤(IRI)相关数据集,并在基因卡片数据库中鉴定缺氧相关基因。数据集合并后,鉴定出在CIRI患者中表达的与缺氧相关的差异表达基因(HRDEGs)。使用在线工具对HRDEGs进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析。对合并后的基因数据集进行基因集富集分析(GSEA)和基因集变异分析(GSVA)。通过最小绝对收缩和选择算子(LASSO)回归分析和支持向量机(SVM)算法构建基于HRDEGs的CIRI诊断模型。通过mRNA-微小RNA(miRNA)相互作用、mRNA-RNA结合蛋白(RBP)网络相互作用、免疫细胞浸润和受试者工作特征(ROC)曲线分析评估9个鉴定出的枢纽基因对CIRI诊断的效能。然后进行逻辑回归分析,并基于9个HRDEGs的表达构建逻辑回归模型。接下来建立列线图并校准预测数据。最后,通过决策曲线分析(DCA)评估构建的逻辑回归模型的临床实用性。本研究揭示了9个具有高诊断价值的关键基因,为CIRI患者的诊断和治疗靶点选择提供了新的见解。:不适用。