Identification and validation of biomarkers linked to T cell proliferation in ischemic stroke

Ischemic stroke (IS) is a major global cause of mortality and chronic disability, with complex immune dysfunction. This study aimed to identify T-cell proliferation-related genes (TRGs) in IS pathogenesis and explore their diagnostic/therapeutic potential. IS patients’ gene expression profiles were obtained from Gene Expression Omnibus (GEO). Differential expression analysis identified differentially expressed genes (DEGs), which overlapped with AmiGO2-derived TRGs to get candidate genes. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) selected biomarkers (with validation). The diagnostic capacity of these biomarkers was evaluated via receiver operating characteristic (ROC) analysis and nomogram development. Gene set enrichment analysis (GSEA) and immune infiltration analyses were done to characterize the biomarkers. Biomarker expression levels were confirmed in clinical samples by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). Both ARG1 and TNFSF13B were consistently upregulated in 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 showed ARG1 positively enriched in CD4 + T cell activation-related sets, TNFSF13B negatively in stemness-related sets. Immune profiling: ARG1 negatively correlated with activated B cells (cor = -0.63, p < 0.001); TNFSF13B 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). The above findings represent preliminary hypothesis-generating evidence and require further validation in larger cohort studies. Overall, this study identified/validated TRG-related IS diagnostic biomarkers, offering insights into immune dysregulation and personalized immunotherapy targets.