Downregulation of N-Myc downstream-regulated gene 4 influences patient survival in gliomas
Downregulation of N-Myc downstream-regulated gene 4 influences patient survival in gliomas
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DOI：
10.1007/s10014-012-0092-2
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发表时间：
2012
影响因子：
3.3
通讯作者：
Shanqu Li;Bo Yang;Gang Li;Shiming He;Yang Li
中科院分区：
文献类型：
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作者：
Shanqu Li;Bo Yang;Gang Li;Shiming He;Yang Li
N-Myc 下游调节基因 4 (NDRG4) 在细胞分化和神经突形成中发挥重要作用。它是已建立的胶质母细胞瘤细胞系和富含癌症干细胞的细胞的细胞周期进展和存活所必需的。本研究的目的是评估神经胶质瘤患者NDRG4表达与临床病理特征和预后的相关性。采用免疫组织化学和蛋白质印迹分析分别研究 128 例神经胶质瘤患者中 NDRG4 蛋白的表达。免疫组织化学显示，与非肿瘤性脑组织相比，神经胶质瘤中NDRG4的表达显着降低（P=0.008），并且其表达随着神经胶质瘤级别的增加而降低。这些结果与Western blot分析的结果一致。此外，非参数分析显示，NDRG4 表达减少与低卡诺夫斯基评分 (P=0.01)、频繁的瘤内坏死 (P=0.03) 和较差的总生存率 (P=0.01) 显着相关。此外，多变量分析显示NDRG4表达（P=0.03）和瘤内坏死（P=0.03）是Cox比例风险模型确定的两个重要的独立预后因素。我们的结果首次提供了令人信服的证据，证明 NDRG4 的表达在人类神经胶质瘤中下调。 NDRG4表达较低的胶质瘤患者预后较差。
N-Myc downstream-regulated gene 4 (NDRG4) plays important roles in cellular differentiation and neurite formation. It is required for cell cycle progression and survival in established glioblastoma cell lines and cancer stem cell-enriched cells. The aim of this study was to evaluate the correlation of NDRG4 expression with the clinicopathological features and prognosis in patients with gliomas. Immunohistochemistry and Western blot analysis were used to investigate the expression of NDRG4 protein, respectively, in 128 patients with gliomas. Immunohistochemistry showed that NDRG4 expression was significantly reduced in glioma relative to nonneoplastic brain tissues (P= 0.008), and that its expression decreased with increasing glioma grade. These results were in line with the results of Western blot analysis. In addition, a non-parametric analysis revealed that the reduced NDRG4 expression was significantly correlated with a low Karnofsky performance score (P= 0.01), frequent intra-tumor necrosis (P= 0.03), and poor overall survival (P= 0.01). Furthermore, multivariate analysis showed that NDRG4 expression (P= 0.03) and intra-tumor necrosis (P= 0.03) were two important independent prognostic factors identified by the Cox proportional hazard model. Our results provide convincing evidence for the first time that the expression of NDRG4 is downregulated in human gliomas. The glioma patients with lower NDRG4 expression have a poor prognosis.