Abstract
<title>Abstract</title> <p>Background For chronic subdural hematoma (CSDH), the involvement of centrosome replication-related genes (CRGs) and their downstream molecular programs remains insufficiently understood. This study aimed to identify CRGs associated with CSDH and infer how they may contribute to disease progression. Methods CSDH-related transcriptomic data and CRG resources were analyzed. Machine learning algorithms were used to select key genes, followed by GSEA and immune infiltration analysis to characterize gene-related functions and their associations with differentially infiltrating immune cells. Regulatory-network analysis and compound prediction were then performed to evaluate possible translational implications. Results Three key genes, ARHGEF10, DTX4, and GADD45A, were identified. GSEA linked ARHGEF10 to the Fas death receptor signaling pathway, DTX4 to the cluster of differentiation 40 (CD40) signaling pathway, and GADD45A to the insulin receptor signaling pathway in cardiomyocytes and additional pathways. Immune infiltration analysis detected three immune cell subsets that differed between CSDH and control samples (P < 0.05): gamma delta T cells, resting memory CD4 T cells, and regulatory T cells. Network analysis predicted 55 transcription factors (TFs) and 64 microRNAs (miRNAs) associated with key-gene regulation, and compound screening yielded 197 candidate compounds, with acetaminophen and benzo[a]pyrene shared across all three genes. Conclusion ARHGEF10, DTX4, and GADD45A were identified as key CRGs potentially involved in CSDH pathogenesis. These findings provide candidate molecular targets and a theoretical basis for mechanistic investigation, diagnostic exploration, and drug development in CSDH.</p>