Exploring histone acetylation in ischemic stroke: CREBBP and CKAP4 as candidate biomarkers linked to histone...

Ischemic stroke (IS) is a severe cerebrovascular disorder. Histone acetylation is a key epigenetic modification that is markedly increased and closely associated with enhanced neuronal tolerance to ischemia. Therefore, identifying biomarkers involved in regulating histone acetylation is critical for elucidating the pathological mechanisms of IS and for developing novel diagnostic and therapeutic strategies.

Transcriptomic data from patients with IS were analyzed to systematically identify the diagnostic biomarkers associated with histone acetylation regulation through an integrative framework combining differential expression analysis, weighted gene co-expression network analysis, multiple machine-learning algorithms, and receiver operating characteristic analysis. Furthermore, the potential biological functions and immune relevance were explored using bioinformatics approaches, including functional enrichment analysis, immune microenvironment evaluation, and disease association analysis. The expression levels of the candidate biomarkers were subsequently validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in clinical blood samples.

A total of 44 histone-acetylation-related differentially expressed genes were identified, among which CREBBP and CKAP4 were confirmed as the key biomarkers in IS. Both genes were enriched in the immune-related pathways, including the complement and coagulation cascades. CREBBP expression showed a negative correlation with CD8⁺ T-cell infiltration, whereas CKAP4 expression was positively associated with M0 macrophage abundance. RT-qPCR analysis confirmed the upregulated expression of these genes in IS samples.

CREBBP and CKAP4 were identified as novel candidate biomarkers whose expression patterns are associated with the histone acetylation regulatory gene networks in IS. These findings highlight the potential involvement of these genes in IS pathogenesis and provide new insights for the development of targeted therapeutic and immunomodulatory strategies.