Pan-cancer analysis of DNMT3A as a robust prognostic biomarker to predict the immunotherapy response

Abstract

Abstract Background DNA methyltransferase 3A (DNMT3A) is essential for de-novo methylation and cell development. Recent studies have shown that dysregulation of methylation regulated by DNMT3A is highly implicated in cancer progression. However, the regulatory roles of DNMT3A in various cancers are not completely clear and need further investigation. Methods The RNA-seq data in The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression databases (GTEx) are the source of this study. Western blot assays were performed to exhibit the relative expression level of DNMT3A in clinical glioma samples. CBioportal was utilized to explore the genomic alternation of DNMT3A. The images of immunofluorescence downloaded from the Human Protein Atlas (HPA) help to show the subcellular distribution of DNMT3A proteins. ComPPI is a powerful tool for studying protein interactions. Single-cell sequencing cohorts from TISCH were used to reveal the DNMT3A expression levels in different cell types. Two types of survival algorithms were conducted to assess the prognostic value of DNMT3A in pan-cancer. Gene Set Enrichment Analysis (GSEA) was applied to explore various cellular pathways and hallmarks. Immune cells infiltration in pan-cancer was summarized using data available on TIMER 2.0 website. Results The expression level of DNMT3A is significantly up-regulated in tumor tissue compared with that in normal tissue in most cancers. DNMT3A is discovered to have great accordance with the immune-related hallmarks like immune response signaling. In addition, the infiltration of DNMT3A in various subtypes of immune cells showed obvious aggregation of Treg, MDSC, B cell, Neutrophil, and Monocyte. At last, the robust prognostic ability of DNMT3A was further enhanced in several independent immunotherapy cohorts.