Upregulation of DLX2 confers a poor prognosis in glioblastoma patients by inducing a proliferative phenotype.
Upregulation of DLX2 confers a poor prognosis in glioblastoma patients by inducing a proliferative phenotype.
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DOI：
10.2174/156652413805076885
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发表时间：
2013-02
影响因子：
2.5
通讯作者：
Zhiguo Yan;Z. Bao;W. Yan;Y-W Liu;C-B Zhang;H. Wang;Y. Feng;Ying Wang;Wei Zhang;G. You;Q-G Zhang;Tao Jiang
中科院分区：
文献类型：
--
作者：
Zhiguo Yan;Z. Bao;W. Yan;Y-W Liu;C-B Zhang;H. Wang;Y. Feng;Ying Wang;Wei Zhang;G. You;Q-G Zhang;Tao Jiang
人类远端无远端同源异型盒(DLX)基因家族编码同源异型盒转录因子，参与调控形态发生和组织内稳态，主要在胚胎发育中表达。最近，DLX基因家族被报道在肿瘤的发生中起重要作用。我们对中国脑胶质瘤基因组图谱(CGGA)组83例多形性胶质母细胞瘤(GBM)患者的全基因组表达基因进行了分析。在mRNA表达谱中确定了两组主要的样本(称为簇1(C1)和簇2(C2))。我们发现在前10个基因本体论术语中，有7个与神经细胞的分化和发育有关。最显著的预后基因是DLX2(P<；0.001，OR=1.744)，DLX2过表达提示83例GBM患者预后不良(低DLX2与高DLX2，77.6vs44.7周，P<；0.001)。来自癌症基因组图谱和MD Anderson癌症中心的关于GBM的mRNA图谱数据的注释显示，神经和神经亚型分别与DLX2的低表达和高表达高度相关。在GBM细胞系LN229中，DLX2基因被敲除后，细胞周期蛋白D1表达下降，细胞增殖减少。总而言之，这些数据表明DLX2的高表达是GBM患者预后不良的标志。
The human Distal-less Homeobox (DLX) gene family encodes homeobox transcription factors involved in the control of morphogenesis and tissue homeostasis, which is primarily expressed in embryonic development. Recently, DLX gene family was reported to have essential roles in carcinogenesis. We have profiled whole genome expressed genes in 83 glioblastoma multiforme (GBM) patients from the Chinese Glioma Genome Atlas (CGGA) Group. Two major groups of samples were identified in mRNA expression profiles (referred to as Cluster 1 (C1) and Cluster 2 (C2)). We identified 7 out of the top 10 Gene Ontology terms in the C1 group were associated with differentiation and development of neuronal cell. The most significant prognostic gene was DLX2 (P < 0.001, OR = 1.744); overexpression of DLX2 indicated poor survival in the 83 GBM patients (low DLX2 vs high DLX2, 77.6 vs 44.7 weeks, P < 0.001). Annotation of mRNA profiling data on GBM from The Cancer Genome Atlas and MD Anderson Cancer Center showed the proneural and neural subtypes highly correlated with low and high DLX2 expression, respectively. Knocking down of DLX2 in GBM cell line-LN229 results in decreased cyclin D1 expression and cell proliferation. Collectively, these data identified high expression of DLX2 as a poor prognostic marker to GBM patients.