Macrophage Polarization-Related Biomarkers in Epilepsy: Integrated Bioinformatics Analysis and Clinical Validation

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Macrophage polarization is increasingly implicated in epilepsy pathogenesis.
• Identifying reliable biomarkers is crucial for understanding epilepsy and developing targeted therapies.

Purpose of the Study:

• To identify macrophage polarization-related genes (MPRGs) as potential biomarkers for epilepsy.
• To investigate the causal roles and immune associations of these MPRGs in epilepsy.
• To validate potential biomarkers in clinical samples.

Main Methods:

• Analysis of publicly available transcriptomic datasets (GEO).
• Integrated bioinformatics approaches including WGCNA, differential expression, machine learning, and ROC curves.
• Two-sample Mendelian randomization (MR) for causal effect assessment.
• Validation of candidate biomarkers at mRNA and protein levels in clinical samples.

Main Results:

• Four MPRGs (DNAH1, PGRMC2, RFX7, TFRC) with strong diagnostic potential for epilepsy were identified.
• DNAH1 showed a putative protective causal association with epilepsy risk via MR.
• Biomarkers exhibited negative associations with macrophage infiltration; cellular distribution varied (DNAH1/PGRMC2 in astrocytes, RFX7 in T cells, TFRC in microglia).
• DNAH1 and TFRC were validated in peripheral blood samples at both transcriptional and protein levels.

Conclusions:

• This study successfully identified MPRGs associated with epilepsy, with DNAH1 and TFRC showing clinical validation.
• DNAH1 demonstrates potential as a protective factor against epilepsy, underscoring its translational relevance.
• The identified MPRGs offer promising avenues for epilepsy biomarker development and therapeutic strategies.