Abstract
Background 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. Methods 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. Results KDM1A 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. Conclusions 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.
Highlights
Epigenetics has been proved as one of the fundamental mechanisms leading towards carcinogenesis [1]. e irregularities of the epigenome associated with cancer are regulated via histone modifications, DNA methylation, chromatin remodeling, and stability of RNA transcripts. e advancement in genomic technologies over the last two decades provided us with a bird’s eye view of the epigenetic factors in oncogenesis, including oncogenic and tumorsuppressor networks
We used the “Survival AnalysisSurvival Map” module of GEPIA2 to obtain the effect of KDM1A expression on overall survival (OS) and disease-free survival (DFS) of various cancers based on TCGA. e highand low-expression cohorts were cut with the ratio of 50 : 50
TIMER2.0 was used to detect the differential expression of KDM1A between tumor and corresponding normal tissues from TCGA. e results showed that KDM1A was highly expressed in 15 cancer types compared with normal samples, including bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and glioblastoma multiforme (GBM), and was lowly expressed only in kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), and kidney renal papillary cell carcinoma (KIRP) (Figure 1(a))
Summary
Epigenetics has been proved as one of the fundamental mechanisms leading towards carcinogenesis [1]. e irregularities of the epigenome associated with cancer are regulated via histone modifications, DNA methylation, chromatin remodeling, and stability of RNA transcripts. e advancement in genomic technologies over the last two decades provided us with a bird’s eye view of the epigenetic factors in oncogenesis, including oncogenic and tumorsuppressor networks. E lysine-specific demethylase 1A (KDM1A), known as LSD1or AOF2, was the first histone demethylation enzyme identified by Shi et al [3]. It revealed the dynamic regulation of histone methylation by both histone methylases and demethylases. KDM1A has been shown to demethylate histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9), which functions in the regulation of gene expression as a transcriptional repressor or activator [3, 4]. Lysine-specific demethylase 1A (KDM1A) is a histone demethylation enzyme and a crucial epigenetic factor for multiple pathological pathways that mediate carcinogenesis and immunogenicity. KDM1A expression was positively correlated with the cancer-associated fibroblasts and myeloid-derived suppressor cells infiltration levels in most cancer types. Our findings provide valuable guidance for further analysis of KDM1A function in pathogenesis and potential clinical treatment
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