Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML.

Integrated bioinformatic analysis of microarray data reveals shared gene signature between MDS and AML.
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微阵列数据的综合生物信息分析揭示了 MDS 和 AML 之间共有的基因特征

DOI:
10.3892/ol.2018.9237
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发表时间:
2018-10
期刊:
影响因子:
2.9
通讯作者:
Li X
Li X
中科院分区:
医学4区
文献类型:
--
作者:
Zhang Z;Zhao L;Wei X;Guo Q;Zhu X;Wei R;Yin X;Zhang Y;Wang B;Li X

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骨髓疾病,特别是骨髓增生异常综合征(MDS)和急性髓性白血病(AML),在世界范围内引起显著的流动性和高死亡率。尽管进行了许多尝试,但MDS和AML发展的共同分子事件仍有待确定。在本研究中,选择了18个微阵列数据集,并进行了荟萃分析,以确定MDS和AML之间共享的基因签名和生物学过程。NetworkAnalyst软件分析发现,MDS和AML中有191个基因表达上调,139个基因表达下调,其中PTH 2 R、TEC和GPX 1表达上调最多,MME、RAG 1和CD 79 B表达下调最多。全面的功能富集分析显示,致癌信号传导相关途径、成纤维细胞生长因子受体(FGFR)和免疫应答相关事件、“白细胞介素-6/干扰素信号传导途径和B细胞受体信号传导途径”分别是上调和下调最多的生物过程。基于网络的荟萃分析确定HSP 90 AA 1和CUL 1是最重要的枢纽基因。有趣的是,我们的研究在很大程度上阐明了MDS和AML之间在潜在途径和遗传标记方面的联系,这揭示了MDS和AML发展和转变的分子机制,并促进了对新的诊断,治疗和预后生物标志物的理解。
Myeloid disorders, especially myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), cause significant mobility and high mortality worldwide. Despite numerous attempts, the common molecular events underlying the development of MDS and AML remain to be established. In the present study, 18 microarray datasets were selected, and a meta-analysis was conducted to identify shared gene signatures and biological processes between MDS and AML. Using NetworkAnalyst, 191 upregulated and 139 downregulated genes were identified in MDS and AML, among which, PTH2R, TEC, and GPX1 were the most upregulated genes, while MME, RAG1, and CD79B were mostly downregulated. Comprehensive functional enrichment analyses revealed oncogenic signaling related pathway, fibroblast growth factor receptor (FGFR) and immune response related events, ‘interleukine-6/interferon signaling pathway, and B cell receptor signaling pathway’, were the most upregulated and downregulated biological processes, respectively. Network based meta-analysis ascertained that HSP90AA1 and CUL1 were the most important hub genes. Interestingly, our study has largely clarified the link between MDS and AML in terms of potential pathways, and genetic markers, which shed light on the molecular mechanisms underlying the development and transition of MDS and AML, and facilitate the understanding of novel diagnostic, therapeutic and prognostic biomarkers.
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