Lactylation-Related Gene Signatures in Intracerebral Hemorrhage: Immune Infiltration, Machine Learning Biomarkers, and Molecular Pathway Insights

INTRODUCTION: Intracerebral hemorrhage (ICH) is a life-threatening neurological disorder with high mortality and limited treatment options. Inflammation and metabolic dysregulation contribute to ICH pathology, yet their molecular underpinnings remain poorly understood. Lactylation, a recently discovered post-translational modification, is known to regulate immune and metabolic pathways. This study investigated lactylation-related genes in ICH, their relationship with immune cell infiltration, and their diagnostic potential. METHODS: Gene expression data from two public datasets (GSE73378 and GSE36791) were integrated after batch correction. Differentially expressed genes (DEGs) were identified with "limma" and lactylation-related genes were curated from the literature. Functional enrichments were conducted via GO and KEGG. Diagnostic genes were selected using XGBoost, Random Forest, and LASSO regression. Immune cell infiltration was analyzed by ssGSEA, and unsupervised clustering defined molecular subtypes. Hemorrhage-associated genes were validated by RT-qPCR in a mouse model of hemorrhage. RESULTS: A total of 111 lactylation-related DEGs were identified. Seven core genes demonstrated strong diagnostic performance (AUC = 0.80-0.92). ssGSEA revealed significant immune alterations associated with lactylation-related gene expression. Unsupervised clustering identified two distinct ICH subtypes with different immune and transcriptional profiles. Upstream regulators predicted PTBP1 and HNRNPD as potential transcriptional regulators. Six of the seven genes were validated in hemorrhagic mice. DISCUSSION: These findings suggest that lactylation links metabolic dysregulation to immune responses in ICH, contributes to molecular heterogeneity, and may enable patient stratification and precision therapeutic strategies. CONCLUSION: Lactylation-related genes are closely linked to immune dysregulation in ICH and show promise as diagnostic biomarkers and therapeutic targets.