Histone acetyltransferase HAT1 drives malignant progression in lower-grade glioma: reshaping the immune microenvironment and molecular mechanisms.

BACKGROUND

HAT1's role in lower-grade glioma (LGG) malignancy and mechanisms is unclear.

METHODS

Multi-omics analysis (TCGA/CGGA transcriptomics, single-cell/spatial transcriptomics, IHC/RT-qPCR) of 906 LGG patients assessed HAT1 expression, prognosis, pathways, immune infiltration, and cellular localization. Molecular docking screened HAT1-targeting drugs.

RESULTS

HAT1 was significantly upregulated in LGG vs. normal brain, correlating with IDH-wildtype status, recurrence, and worse overall survival (independent risk factor). It specifically enriched malignant cell regions. HAT1 overexpression activated cell cycle, adherens junctions, and RIG-I-like signaling. It promoted immune cell infiltration and checkpoint expression. Top FDA-approved compounds with strong binding affinity were identified.

CONCLUSIONS

HAT1 drives LGG malignancy by remodeling the immune microenvironment and activating key oncogenic pathways. Its spatial enrichment in malignant niches and druggability provide a novel basis for targeted-immunotherapy combinations.