Unraveling the molecular interplay of ferroptosis and immune regulation in stroke pathogenesis: A comprehensive bioinformatics analysis

Abstract

Neurological disorders, particularly stroke, pose significant public health challenges, prompting a comprehensive investigation into the intricate interplay between ferroptosis and immune responses. This study aims to uncover the molecular mechanisms of stroke, emphasizing the connection between ferroptosis and immune regulation. Objectives include identifying differentially expressed genes in stroke patients, assessing immune cell subtype activation, employing advanced predictive modeling to pinpoint key candidate genes such as STMN1 and ATG16L1, exploring associations with immune cell subtypes, and revealing critical pathways, such as matrix degradation and inflammatory responses, activated in stroke through Gene Set Variation Analysis (GSVA). A comprehensive approach was adopted, involving differential gene expression analysis, functional enrichment analysis, weighted gene co-expression network analysis, Lasso regularization, random forest models, and the CIBERSORT (https://cibersortx.stanford.edu) algorithm, to assess immune cell subtypes. The study pinpointed genes with significant expression differences in stroke patients, highlighting the activation of Th17 cells and the NF-κ B signaling pathway. Key candidate genes, including STMN1 and ATG16L1, were identified using advanced predictive modeling. The relative abundance of immune cell subtypes, particularly natural killer cells (NK cells) and T cell subgroups, was associated with stroke through CIBERSORT. GSVA uncovered the activation of critical biological pathways such as matrix degradation and inflammatory responses. The analysis pinpointed STMN1 and ATG16L1 as robust predictors, emphasizing their potential as therapeutic targets. Th17 cells and the NF-κ B signaling pathway emerged as pivotal contributors to stroke pathogenesis. Notably, NK cells and specific T cell subgroups demonstrated significant associations with stroke. GSVA further illuminated the activation of key pathways, providing deeper insights into the biological processes underlying stroke. This study sheds light on crucial genes and pathways implicated in stroke, emphasizing the roles of ferroptosis and immune cell subtypes. The identified genes and pathways offer promising avenues for targeted therapeutic interventions in stroke, with a broader implication for advancing neurological disorder treatments through innovative perspectives on ferroptosis and immune regulation.