Abstract
BackgroundAcute myelogenous leukemia (AML) is a common pediatric malignancy in children younger than 15 years old. Although the overall survival (OS) has been improved in recent years, the mechanisms of AML remain largely unknown. Hence, the purpose of this study is to explore the differentially methylated genes and to investigate the underlying mechanism in AML initiation and progression based on the bioinformatic analysis.MethodsMethylation array data and gene expression data were obtained from TARGET Data Matrix. The consensus clustering analysis was performed using ConsensusClusterPlus R package. The global DNA methylation was analyzed using methylationArrayAnalysis R package and differentially methylated genes (DMGs), and differentially expressed genes (DEGs) were identified using Limma R package. Besides, the biological function was analyzed using clusterProfiler R package. The correlation between DMGs and DEGs was determined using psych R package. Moreover, the correlation between DMGs and AML was assessed using varElect online tool. And the overall survival and progression-free survival were analyzed using survival R package.ResultsAll AML samples in this study were divided into three clusters at k = 3. Based on consensus clustering, we identified 1,146 CpGs, including 40 hypermethylated and 1,106 hypomethylated CpGs in AML. Besides, a total 529 DEGs were identified, including 270 upregulated and 259 downregulated DEGs in AML. The function analysis showed that DEGs significantly enriched in AML related biological process. Moreover, the correlation between DMGs and DEGs indicated that seven DMGs directly interacted with AML. CD34, HOXA7, and CD96 showed the strongest correlation with AML. Further, we explored three CpG sites cg03583857, cg26511321, cg04039397 of CD34, HOXA7, and CD96 which acted as the clinical prognostic biomarkers.ConclusionOur study identified three novel methylated genes in AML and also explored the mechanism of methylated genes in AML. Our finding may provide novel potential prognostic markers for AML.
Highlights
Acute myelogenous leukemia (AML) is a common pediatric hematologic cancer in children younger than 15 years [1, 2]
Scholars have found that cisplatin resistance is related to the hypermethylation deletion of several CpG sites mainly located in the intergenomic region, which directly affects the efficacy of treatment, affecting the survival time of patients [15]
Besides DNA methylation being strongly associated with prognosis of AML patients, it has been reported that different methylation types have different clinical outcomes for AML patients [23]
Summary
Acute myelogenous leukemia (AML) is a common pediatric hematologic cancer in children younger than 15 years [1, 2]. Previous studies found that azacitidine and decitabine act as the inhibitors of DNA methylation and have been used in chemotherapy in patients with AML [20, 21]. Inhibiting the expression of DNA methylation can effectively improve the effect of chemotherapy and prolong the survival time of AML patients [22]. Previous studies have found that DNA methylation is a high sensitivity and specificity biomarker of AML in distinguishing it from other leukemia [9]. Acute myelogenous leukemia (AML) is a common pediatric malignancy in children younger than 15 years old. The purpose of this study is to explore the differentially methylated genes and to investigate the underlying mechanism in AML initiation and progression based on the bioinformatic analysis
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