Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.

中文翻译：

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人类癌症中 HAT 和 HDAC 的综合表征揭示了它们在免疫检查点阻断中的作用

组蛋白乙酰化由两个相互拮抗的酶家族——组蛋白乙酰转移酶（HAT）和组蛋白脱乙酰酶（HDAC）控制，作为控制转录的主要表观遗传机制之一，其异常调节与癌症的各个方面有关。然而，对于癌症中的 HDAC 和 HAT 的全面了解仍然缺乏。基于下一代序列数据对 33 种癌症类型进行系统分析，揭示了不同癌症类型中 HDAC 和 HAT 的异质表达模式。特别是，HDAC10 和 HDAC6 在大多数癌症中表现出显着的下调。泛癌的主成分分析（PCA）揭示了正常组织与肿瘤邻近正常组织之间HDAC和HAT的显着差异。HDACs和HATs的异常表达部分归因于多种类型癌症中的CNV和DNA甲基化。HDAC 和 HAT 的预后意义（AUC 达到 0.736）显示了 KIRC 中的五基因特征，包括 KAT2A、HAT1、KAT5、CREBBP 和 SIRT1。NCI-60 药物数据库分析表明，多种药物的细胞毒性作用与 HDAC 和 HAT 表达失调有关。免疫浸润和免疫治疗的分析表明，KAT2B和HDAC9与免疫浸润和免疫治疗相关。我们的分析提供了对 HDAC 和 HAT 在泛癌中的调节和影响的全面了解。这些发现为未来癌症发展和治疗中潜在的个体 HDAC 和 HAT 的生物学研究提供了新的证据。