HDAC 家族成员是多种癌症预测性生物标志物，调节肿瘤发生。然而，在颅内室管膜瘤（EPN）的生物学中，这些基因的作用仍未被探索。本研究分析了 EPN 转录组数据集中的 18 个 HDAC 基因，在颞上隆 ZFTA 融合（ST-ZFTA）与颞上隆 YAP1 融合和后颅凹 EPN 中，发现 HDAC4 显著升高，而 HDAC7 和 SIRT2 降低在 ST-ZFTA 中。单细胞 RNA-Seq、实时定量 PCR 和免疫组织化学分析也发现 HDAC4 在 ST-ZFTA 中高表达。生存分析显示，在 HDAC4 和 SIRT1 mRNA 水平较高的 EPN 中，预后较差。本体富集分析显示，HDAC4 高水平标志与病毒过程一致，而含胶原质基质和细胞间连接物的 HDAC4 低水平标志富集。免疫基因分析表明，HDAC4 表达与自然杀伤静息细胞水平低相关。通过计算机辅助预测分析，预测了针对 HDAC4 和 ABCG2 的多种小分子化合物对 HDAC4 高表达 ZFTA 有效。本研究结果为颅内室管膜瘤中 HDAC 家族的生物学提供了新的见解，并揭示了 HDAC4 作为 ST-ZFTA 的预后标记和潜在治疗靶点。 © 2023 作者，独家授权 Springer Nature America，Inc.

Members of the HDAC family are predictive biomarkers and regulate the tumorigenesis in several cancers. However, the role of these genes in the biology of intracranial ependymomas (EPNs) remains unexplored. Here, an analysis of eighteen HDACs genes in an EPN transcriptomic dataset, revealed significantly higher levels of HDAC4 in supratentorial ZFTA fusion (ST-ZFTA) compared with ST-YAP1 fusion and posterior fossa EPNs, while HDAC7 and SIRT2 were downregulated in ST-ZFTA. HDAC4 was also overexpressed in ST-ZFTA as measured by single-cell RNA-Seq, quantitative real time-polymerase chain reaction, and immunohistochemistry. Survival analyses showed a significantly worse outcome for EPNs with higher HDAC4 and SIRT1 mRNA levels. Ontology enrichment analysis showed an HDAC4-high signature consistent with viral processes while collagen-containing extracellular matrix and cell-cell junction were enriched in those with an HDAC4-low signature. Immune gene analysis demonstrated a correlation between HDAC4 expression and low levels of NK resting cells. Several small molecules compounds targeting HDAC4 and ABCG2, were predicted by in silico analysis to be effective against HDAC4-high ZFTA. Our results provide novel insights into the biology of the HDAC family in intracranial ependymomas and reveal HDAC4 as a prognostic marker and potential therapeutic target in ST-ZFTA.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.