HAT1 regulates the immune microenvironment and promotes the malignant pathology of lower-grade gliomas

Abstract

Histone acetyltransferase 1 (HAT1) is a key regulatory molecule in histone acetylation and promotes cancer malignancy. This study aimed to reveal the role of HAT1 in lower-grade gliomas (LGGs) and the potential mechanism by which it mediates pathological processes. We collected transcriptome data and detailed clinicopathological features of 906 LGG patients through TCGA RNA-seq and CGGA RNA-seq. Subsequently, various bioinformatics and molecular biology methods were used to reveal the impact of HAT1 on the prognosis, clinical characteristics, regulatory mechanism, and the potential value of antitumor immunotherapy in patients with LGG. RT-qPCR and immunohistochemistry showed that the expression level of HAT1 protein or mRNA in LGG tissue was significantly higher than that in non-tumor brain tissue. Furthermore, there is a positive expression relationship between HAT1 and clinical malignant patient characteristics such as IDH-wild and recurrent types. Kaplan–Meier and Cox regression revealed that high HAT1 expression could be used as an independent risk factor for reduced overall survival of patients. GSEA analysis showed that HAT1 overexpression promotes the activation of the cell cycle, adherens junctions, and RIG-I-like receptor signaling pathways in LGG. Finally, the TIMER database showed that HAT1 could promote the increase in multiple immune cell infiltration levels and showed a positive expression relationship with immune checkpoints in LGG. This study provides a potentially high-value target for the antitumor immunotherapy of LGG patients. For the first time, we explain the influence and mechanism of HAT1 on the prognosis of LGG patients to gain insights into the pathogenesis of LGG.