Identification of the Molecular Subtypes of Acute Ischemic Stroke Using Bioinformatics and Machine Learning

Abstract Acute ischemic stroke (AIS) is a severe disorder characterized by complex pathophysiological processes, which can lead to disability and death. This study aimed to determine necroptosis-associated genes in Acute ischemic stroke (AIS) and to investigate their potential as diagnostic and therapeutic targets for AIS. Expression profiling data were acquired from the Gene Expression Omnibus database, and necroptosis-associated genes were retrieved from GeneCards. The differentially expressed genes (DEGs) and necroptosis-related genes were intersected to obtain the necroptosis-related DEGs (NRDEGs) in AIS. In AIS, a total of 76 genes associated with necroptosis (referred to as NRDEGs) were identified. Enrichment analysis of these genes revealed that they were primarily enriched in pathways known to induce necroptosis. Using Weighted gene co-expression network analysis (WGCNA), five co-expression modules consisting of NRDEGs were identified, along with two modules that exhibited a strong correlation with AIS. Protein-protein interaction (PPI) analysis resulted in the identification of 20 hub genes. The Least absolute shrinkage and selection operator (LASSO) regression model demonstrated promising potential for diagnostic prediction. The receiver operating characteristic (ROC) curve validated the diagnostic model and selected nine characteristic genes that exhibited statistically significant differences (p < 0.05). By employing consensus clustering, distinct patterns of necroptosis were identified using these nine signature genes. The results were verified by quantitative PCR (qPCR) in HT22 cells and an external data set. Furthermore, the analyzed ceRNA network included nine lncRNAs, six miRNAs, and three mRNAs. Overall, this study offers novel insights into the molecular mechanisms underlying NRDEGs in AIS. The findings provide valuable evidence and contribute to our understanding of the disease.