Identification of key pathways and genes in TP53 mutation acute myeloid leukemia: evidence from bioinformatics analysis

被引:17
|
作者
Huang, Rui [1 ]
Liao, Xiwen [2 ]
Li, Qiaochuan [1 ]
机构
[1] Guangxi Med Univ, Affiliated Hosp 1, Dept Hematol, 6 Shuang Yong Rd, Nanning 530021, Guangxi, Peoples R China
[2] Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Nanning, Guangxi, Peoples R China
来源
ONCOTARGETS AND THERAPY | 2018年 / 11卷
基金
中国国家自然科学基金;
关键词
bioinformatics analysis; acute myeloid leukemia; TCGA; RNA sequencing; TP53; mutation; ACUTE MYELOGENOUS LEUKEMIA; FALSE DISCOVERY RATE; DIFFERENTIAL EXPRESSION ANALYSIS; PROTEIN-INTERACTION NETWORKS; CELL-ADHESION MOLECULES; E-CADHERIN EXPRESSION; PI3K/AKT PATHWAY; DRUG-RESISTANCE; GROWTH-FACTOR; MYELODYSPLASTIC SYNDROMES;
D O I
10.2147/OTT.S156003
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Tumor protein p53 (TP53) mutations are not only a risk factor in acute myeloid leukemia (AML) but also a potential biomarker for individualized treatment options. This study aimed to investigate potential pathways and genes associated with TP53 mutations in adult de novo AML. Methods: An RNA sequencing dataset of adult de novo AML was downloaded from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified by edgeR of the R platform. Key pathways and genes were identified using the following bioinformatics tools: gene set enrichment analysis (GSEA), gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection. Results: GSEA suggested that TP53 mutations were significantly associated with cell differentiation, proliferation, cell adhesion biological processes, and MAPK pathway. In total, 1,287 genes were identified as DEGs. GO and KEGG analysis suggested that upregulation of DEGs was significantly enriched in categories associated with cell adhesion biological processes, Ras-associated protein 1, PI3K-Akt pathway, and cell adhesion molecules. The top ten genes ranked by degree, CDH1, BMP2, KDR, LEP, CASR, ITGA2B, APOE, MNX1, NMU, and TRH, were identified as hub genes from the protein-protein interaction network. Survival analysis suggested that patients with TP53 mutations had a significantly increased risk of death, while the mRNA expression level in patients with TP53 mutation was similar to those carrying TP53 wild type. Conclusion: Our findings have indicated that multiple genes and pathways may play a crucial role in TP53 mutation AML, offering candidate targets and strategies for TP53 mutation AML individualized treatment.
引用
收藏
页码:163 / 173
页数:11
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