Identification of Key Genes and Pathways Associated with RUNX1 Mutations in Acute Myeloid Leukemia Using Bioinformatics Analysis.
Identification of Key Genes and Pathways Associated with RUNX1 Mutations in Acute Myeloid Leukemia Using Bioinformatics Analysis.
复制标题
利用生物信息学分析鉴定与急性髓系白血病 RUNX1 突变相关的关键基因和通路
DOI：
10.12659/msm.910916
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发表时间：
2018-10-05
期刊：
影响因子：
--
通讯作者：
Lai Y
中科院分区：
文献类型：
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作者：
Zhu F;Huang R;Li J;Liao X;Huang Y;Lai Y
RUNXl在造血过程中起关键调节作用，并且是人急性白血病中多染色体易位的常见靶标。RUNX 1基因突变可导致急性白血病的发生，并影响AML患者的预后。我们的目的是确定与RUNX 1突变的急性髓细胞白血病（AML）患者相关的关键基因和通路，并探索可能的分子标记物，以寻找该疾病的新治疗靶点。从癌症基因组图谱数据库获得151例AML的RNA测序数据集。使用R平台的edgeR鉴定差异表达基因（DEG）。使用ProteinterONE分析PPI（蛋白质-蛋白质相互作用）网络聚类模块，并对模块进行KEGG（京都基因和基因组百科全书）途径富集分析。共有379个基因被鉴定为DEG。DEG的KEGG富集分析显示在癌症中显著富集的途径，细胞外基质（ECM）-受体相互作用途径和环磷酸腺苷（cAMP）信号传导途径。按程度排列的前10个基因是PRKACG、ANKRD 7、RNFL 7、ROPN 11、TEX 14、PRMT 8、OTOA、CFAP 99、NRXN 1和DMRT 1，它们被鉴定为来自蛋白质-蛋白质相互作用网络（PPI）的枢纽基因。统计分析显示，与未发生RUNX 1突变的患者相比，发生RUNX 1突变的AML患者的中位生存时间（MST）较短，临床结局较差，死亡风险增加。本研究中确定的DEG和通路将有助于了解AML中RUNX 1突变的分子机制，并为RUNX 1突变AML制定有效的治疗策略。
RUNXl plays a key regulatory role in the process of hematopoiesis and is a common target for multiple chromosomal translocations in human acute leukemia. Mutations of RUNX1 gene can lead to acute leukemia and affect the prognosis of AML patients. We aimed to identify pivotal genes and pathways involved in RUNX1-mutated patients of with acute myeloid leukemia (AML) and to explore possible molecular markers for novel therapeutic targets of the disease. The RNA sequencing datasets of 151 cases of AML were obtained from the Cancer Genome Atlas database. Differentially expressed genes (DEGs) were identified using edgeR of the R platform. PPI (protein–protein interaction) network clustering modules were analyzed with ClusterONE, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses for modules were performed. A total of 379 genes were identified as DEGs. The KEGG enrichment analysis of DEGs showed significantly enriched pathways in cancer, extracellular matrix (ECM)-receptor interaction pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway. The top 10 genes ranked by degree were PRKACG, ANKRD7, RNFL7, ROPN11, TEX14, PRMT8, OTOA, CFAP99, NRXN1, and DMRT1, which were identified as hub genes from the protein–protein interaction network (PPI). Statistical analysis revealed that RUNX1-mutated patients with AML had a shorter median survival time (MST) with poor clinical outcome and an increased risk of death when compared with those without RUNX1 mutations. DEGs and pathways identified in the present study will help understand the molecular mechanisms underlying RUNX1 mutations in AML and develop effective therapeutic strategies for RUNX1-mutation AML.