Abstract:
Background: Histone deacetylase (HDAC) plays a crucial role in regulating the expression and activity of a variety of genes associated with tumor progression and immunotherapeutic processes. The aim of this study was to characterize HDAC pathway copy number variation (CNV) in pan-cancer. Methods: A total of 10,678 tumor samples involving 33 types of tumors from The Cancer Genome Atlas (TCGA) were included in the study. Results: HDAC pathway CNV and CNV gain were identified as prognostic risk factors for pan-cancer species. The differences of tumor characteristics including tumor mutational burden, tumor neoantigen burden, high-microsatellite instability, and microsatellite stable between HDAC pathway CNV altered-type group and wild-type group varied among the various cancer species. In some cancer types, HDAC pathway CNV alteration was positively correlated with loss of heterozygosity, CNV burden, ploidy, and homologous recombination defect score markers, while it was significantly negatively correlated with immune score and stroma score. There were significant differences in immune characteristics such as major histocompatibility complex class I (MHC-I), MHC-II, chemokines, cytolytic-activity, and IFN-γ between the two groups. Immune cycle characteristics varied from one cancer type to another. Conclusion: This study reveals a tumor and immune profile of HDAC pathway CNV as well as its unlimited potential in immune prognosis.
摘要:
背景:组蛋白去乙酰化酶(HDAC)在调节与肿瘤进展和免疫治疗过程相关的多种基因的表达和活性中起着至关重要的作用。这项研究的目的是表征泛癌中的HDAC途径拷贝数变异(CNV)。方法:本研究共纳入来自癌症基因组图谱(TCGA)的10,678例肿瘤样本,涉及33种肿瘤。结果:HDAC途径CNV和CNV增益被确定为泛癌症物种的预后危险因素。肿瘤特征的差异包括肿瘤突变负荷、肿瘤新抗原负荷,微小卫星的不稳定性,HDAC途径CNV改变型组和野生型组之间的微卫星稳定性在各种癌症物种之间有所不同。在某些癌症类型中,HDAC通路CNV改变与杂合性缺失呈正相关,CNV负担,倍性,和同源重组缺陷评分标记,而与免疫评分和基质评分呈显著负相关。主要组织相容性复合体I类(MHC-I)等免疫特性存在显著差异,MHC-II,趋化因子,细胞溶解活性,两组之间的IFN-γ。免疫周期特征因癌症类型而异。结论:这项研究揭示了HDAC途径CNV的肿瘤和免疫特征及其在免疫预后中的无限潜力。