Exploring Histone Acetylation in Ischemic Stroke: The Role of CREBBP and CKAP4 as Key Biomarkers

Abstract Background Ischemic stroke (IS) is a serious cerebrovascular disease. Excessive acetylated protein levels are linked to neuronal resistance to ischemia, making histone acetylation regulatory-related biomarkers crucial for IS. Methods To identify differentially expressed genes (DEGs) in GSE16561, differential expression analysis (normal versus IS) was performed. Key module genes linked to single-sample gene set enrichment analysis (ssGSEA) scores of histone acetylation regulatory-related genes (HARGs) were identified via weighted correlation network analysis (WGCNA). Overlapping DEGs and key module genes yielded histone acetylation regulatory-related DEGs (HAR-DEGs). Three machine learning algorithms, expression, and receiver operating characteristic (ROC) analysis screened histone acetylation regulatory-related biomarkers. Functional enrichment, immune microenvironment analysis, and disease association were conducted. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) assessed biomarker expression levels. Results A total of 550 differentially DEGs and 137 key module genes related to ssGSEA enrichment scores of HARGs were identified. Overlapping these yielded 44 HAR-DEGs. CREBBP and CKAP4 were identified as histone acetylation regulatory-related biomarkers in IS. Both biomarkers were linked to immune-related pathways, such as complement and coagulation cascades. CREBBP inversely correlated with CD8+ T cell scores, while CKAP4 positively correlated with M0 macrophage scores. Both were associated with brain injury and disease. RT-qPCR confirmed elevated expression of CREBBP and CKAP4 in IS samples compared to controls. Conclusion In summary, we identified two biomarkers (CREBBP and CKAP4) linked to histone acetylation regulation in IS, providing a theoretical basis for its treatment.