Li Lingyue, Wang Yiyu, Mou Yuan, Wu Hao, Qin Ye
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, Hubei Province, China.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Can J Infect Dis Med Microbiol. 2021 Dec 9;2021:4668565. doi: 10.1155/2021/4668565. eCollection 2021.
Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. Although increasing evidence supposes the association between KDM1A and cancers, no systematic multi-omics analysis of KDM1A is available.
We systematically evaluated the KDM1A expression of various cancer and normal tissues and the unique relationship between KDM1A expression and prognosis of cancer cases based on The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The genetic variations, phosphorylation, and DNA methylation of KDM1A were analyzed via various tools. We further analyzed the correlation of KDM1A expression and fibroblasts and immune cell infiltration score of TCGA samples via TIMER2.0.
was highly expressed in 17 types of total 33 cancers, while it expressed low levels in only 4 cancers. High KDM1A expression was associated with worse survival status in various cancers. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Additionally, KDM1A in most cancer types was negatively correlated with Th1 cell infiltration and positively correlated with Th2 cells. Moreover, spliceosome, cell cycle, and RNA transport pathways were involved in the functional mechanisms of KDM1A via enrichment analysis.
Our study describes the epigenetic factor KDM1A as an oncogene and prognostic biomarker. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment.
赖氨酸特异性去甲基化酶1A（KDM1A）是一种组蛋白去甲基化酶，是介导致癌作用和免疫原性的多种病理途径的关键表观遗传因子。尽管越来越多的证据表明KDM1A与癌症之间存在关联，但尚无关于KDM1A的系统多组学分析。
我们基于癌症基因组图谱（TCGA）、基因型组织表达（GTEx）和临床蛋白质组肿瘤分析联盟（CPTAC）数据库，系统评估了各种癌症和正常组织中KDM1A的表达，以及KDM1A表达与癌症病例预后之间的独特关系。通过各种工具分析了KDM1A的基因变异、磷酸化和DNA甲基化情况。我们还通过TIMER2.0进一步分析了TCGA样本中KDM1A表达与成纤维细胞和免疫细胞浸润评分的相关性。
在总共33种癌症中的17种中高表达，而在仅4种癌症中低表达。KDM1A高表达与各种癌症中较差的生存状态相关。在大多数癌症类型中，KDM1A表达与癌症相关成纤维细胞和髓源性抑制细胞浸润水平呈正相关。此外，在大多数癌症类型中，KDM1A与Th1细胞浸润呈负相关，与Th2细胞呈正相关。此外，通过富集分析发现剪接体、细胞周期和RNA转运途径参与了KDM1A的功能机制。
我们的研究将表观遗传因子KDM1A描述为一种癌基因和预后生物标志物。我们的发现为进一步分析KDM1A在发病机制中的功能和潜在临床治疗提供了有价值的指导。
