Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, 253# Gongye Road, Guangzhou, China.
The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
J Neurooncol. 2017 Sep;134(2):397-405. doi: 10.1007/s11060-017-2539-0. Epub 2017 Jul 27.
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.
越来越多的证据表明,离子通道不仅调节可兴奋细胞中的电信号,而且在人类癌症的发生中也起着重要作用。然而,离子通道在神经胶质瘤中的作用仍存在争议。我们使用全基因组 mRNA 表达谱对中国神经胶质瘤患者进行了系统的离子通道基因表达模式分析。首先,使用 Spearman 秩相关检验在肿瘤分级和基因表达之间进行分析,确定了由 47 个离子通道基因组成的分子特征(IC47)。我们根据 IC47 为每个神经胶质瘤患者分配了风险评分。我们证明了该风险评分可以有效地预测神经胶质瘤患者的总生存期。接下来,我们在不同的分子神经胶质瘤亚型中筛选了 IC47。IC47 表现出间充质亚型和野生型 IDH1 的偏好。GO 分析和 GSVA 对 IC47 的功能注释表明,高风险评分的患者倾向于表现出与细胞凋亡和细胞黏附相关的蛋白表达降低,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,离子通道基因表达可以提高神经胶质瘤的分子水平的亚型分类。本研究中的发现已在两个独立的队列中得到验证。