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

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.