Comprehensive DNA Methylation-transcriptome Profiles Association Analysis During the Treatment of Acute Myelocytic Leukemia

Abstract

Background: Epigenetic modifications have recently attracted much attention in the study of the biological mechanisms of Acute Myelocytic Leukemia (AML) for therapy and prognosis. However, studies on DNA methylation changes during AML treatment are limited. Objective: The comprehensive DNA methylation-transcriptome profiles association analysis in this study aimed to establish whole-genome DNA methylation profiles and explore DNA methylation-related genes and their potential functions before and after treatment. And more appropriate biomarkers are expected to be identified for therapy strategies in AML. Methods: Illumina 450K and RNA-Seq data were obtained from the Cancer Genome Atlas. We performed comprehensive DNA methylation-transcriptome profiles association analysis, pathway analysis, correlation analysis, and survival analyses. The StarBase database was utilized to predict interactions between lncRNAs, miRNAs and target mRNAs. Results: In total, 1592 distinct CpG sites and 2419 different expression transcripts were identified between pretreatment and post-treatment AML. The significantly enriched functions of methylated genes were stem cell differentiation, cell population maintenance, and cell development. The expression of UGT3A2, MOG, and VSTM1 was correlated with DNA methylation levels (r2 >0.5). Lastly, we identified 4 lncRNAs, 9 miRNAs and 142 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network. Conclusion: Our results revealed that DNA methylation was altered before and after treatment. Alterations in DNA methylation affected target gene expression and participated in the key biological processes of AML. Therefore, ceRNA networks may provide further insight into the study of favorable therapeutic markers in AML.