Identification and validation of T cell proliferation-associated transcriptomic biomarkers in ischemic stroke

Ischemic stroke (IS) is a major global cause of mortality and chronic disability and is associated with complex immune dysfunction. This study aimed to identify T cell proliferation-related genes (TRGs) associated with IS pathogenesis and to identify T cell proliferation-related transcriptomic biomarkers associated with IS and evaluate their ability to distinguish IS from controls. Gene expression profiles from patients with IS were obtained from the Gene Expression Omnibus. Candidate genes were identified through differential expression analysis by determining differentially expressed genes that overlapped with AmiGO2-derived TRGs. Least Absolute Shrinkage and Selection Operator regression and Support Vector Machine-Recursive Feature Elimination selected biomarkers (with validation). The diagnostic performance of these biomarkers was evaluated using receiver operating characteristic analysis and nomogram development. Gene set enrichment analysis (GSEA) and immune infiltration analyses were performed to characterize the identified biomarkers. Biomarker expression levels were confirmed in clinical samples by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). ARG1 and TNFSF13B were consistently upregulated in patients with IS across cohorts and demonstrated strong diagnostic performance (area under the curve [AUC] > 0.7). The AUC for the nomogram model reached 0.92, suggesting favorable predictive performance that warrants further validation. GSEA revealed that ARG1 was positively enriched in CD4 + T cell activation-related sets, while TNFSF13B was negatively enriched in stemness-related sets. The immune profiling revealed that ARG1 was negatively correlated with activated B cells (cor = − 0.63, p < 0.001) and TNFSF13B was inversely associated with activated CD8 + T cells (cor = − 0.34, p < 0.01). RT-qPCR confirmed their higher expression in IS vs controls ( p < 0.05). These findings support ARG1 and TNFSF13B as candidate TRG-related transcriptomic biomarkers for distinguishing IS from controls and provide hypothesis-generating insights into their immune-related biological functions. Given the small RT-qPCR cohort, the experimental validation should be considered preliminary, and larger clinically stratified cohorts are required to further confirm their diagnostic value and biological relevance.