Prognostic value of ion channel genes in Chinese patients with gliomas based on mRNA expression profiling

Prognostic value of ion channel genes in Chinese patients with gliomas based on mRNA expression profiling
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基于mRNA表达谱的离子通道基因对中国胶质瘤患者的预后价值

DOI:
10.1007/s11060-017-2539-0
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发表时间:
2017-07
影响因子:
3.9
通讯作者:
Zhang Shi-Zhong
Zhang Shi-Zhong
中科院分区:
医学2区
文献类型:
--
作者:
Lu Feng-fei;Wang Hao-Yuan;He Xiao-zheng;Liang Ting-Yu;Wang Wen;Hu Hui-Min;Wu Fan;Liu Yan-Wei;Zhang Shi-Zhong

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越来越多的证据表明,离子通道不仅调节可兴奋细胞的电信号,而且在人类癌症的发生发展中起着重要作用。然而,离子通道在胶质瘤中的作用仍然存在争议。我们利用全基因组mRNA表达谱系统地分析了一组中国脑胶质瘤患者离子通道基因的表达模式。首先,通过对肿瘤分级和基因表达进行Spearman等级相关检验,确定了一个包含47个离子通道基因(IC47)的分子特征。我们根据IC47为每个胶质瘤患者分配了一个风险评分。我们证明风险评分有效地预测了胶质瘤患者的总体生存。接下来,我们在不同的分子胶质瘤亚型中筛选IC47。IC47表现为间充质亚型和野生型IDH1。基因本体论(GO)分析和IC47功能注释的基因集变异分析(GSVA)显示,高危评分的患者往往表现出与细胞凋亡和细胞黏附相关的蛋白表达降低,而与细胞周期和细胞增殖相关的蛋白表达增加。这些结果表明,离子通道基因的表达可以在分子水平上改善胶质瘤的亚型分类。本研究中的发现已经在两个独立的队列中得到了验证。
Increasing evidence suggests that ion channels not only regulate electric signaling in excitable cells but also play important roles in the development of human cancer. However, the roles of ion channels in glioma remain controversial. We systematically analyzed the expression patterns of ion channel genes in a cohort of Chinese patients with glioma using whole-genome mRNA expression profiling. First, a molecular signature comprising 47 ion channel genes (IC47) was identified using Spearman’s rank correlation test conducted between tumor grade and gene expression. We assigned a risk score based on IC47 to each glioma patient. We demonstrated that the risk score effectively predicted overall survival in glioma patients. Next, we screened IC47 in different molecular glioma subtypes. IC47 showed a Mesenchymal subtype and wild-type IDH1 preference. Gene ontology (GO) analysis and gene set variation analysis (GSVA) for the functional annotation of IC47 showed that patients with high-risk scores tended to exhibit the decreased expression of proteins associated with the apoptosis and cell adhesion, and higher expression of proteins associated with the cell cycle and cell proliferation. These results suggest that ion channel gene expression could improve the subtype classification in gliomas at the molecular level. The findings in the present study have been validated in two independent cohorts.
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