ArticleJournal of inflammation research2026
Macrophage Polarization-Related Biomarkers in Epilepsy: Integrated Bioinformatics Analysis and Clinical Validation.
Article in Journal of inflammation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Purpose: Accumulating evidence implicates macrophage polarization in the pathogenesis of epilepsy. This study integrated bioinformatics and experimental approaches to identify macrophage polarization-related genes (MPRGs) as potential biomarkers and to elucidate their putative causal roles and immune associations in epilepsy. Patients and Methods: Publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO; GSE143272, GSE88992, and GSE201048) were analyzed. Macrophage polarization-related biomarkers with diagnostic potential were identified via integrated analyses, including immune infiltration, weighted gene co-expression network analysis (WGCNA), differential expression, machine learning algorithms, expression profiling, and receiver operating characteristic (ROC) curves. Two-sample Mendelian randomization (MR) was performed to assess the causal effects on epilepsy. Biomarker-immune cell associations and single-cell expression patterns were analyzed, and biomarker expression was validated at transcriptional (mRNA) and protein levels in clinical samples. Results: Integrated analyses identified four macrophage polarization-related candidate biomarkers for epilepsy-DNAH1, PGRMC2, RFX7, and TFRC-all exhibiting strong diagnostic performance. Two-sample MR suggested a putative protective causal association between genetically predicted DNAH1 expression and epilepsy risk (OR < 1, P < 0.05). All four biomarkers showed negative associations with macrophage infiltration, and single-cell analysis demonstrated their cellular distribution patterns, with DNAH1 and PGRMC2 mainly detected in astrocytes, RFX7 in T cells, and TFRC in microglia. Among the four candidate biomarkers identified through integrated bioinformatics analyses, DNAH1 and TFRC were further validated in peripheral blood samples at both the transcriptional and protein levels. Conclusion: This study identified macrophage polarization-related candidate biomarkers associated with epilepsy through integrated bioinformatics analyses. Among them, DNAH1 and TFRC were supported by clinical blood-based validation, with DNAH1 showing a putative protective causal role, highlighting their potential translational relevance in epilepsy.
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