摘要目的探 讨核糖体结合糖蛋白2(RPN2)在脑胶质瘤中的表达模式,以及其与患者的临床特征及预后的关系.方法 回顾性分析309例来自中国脑胶质瘤基因组图谱数据库(CGGA)的脑胶质瘤患者的临床资料及其mRNA测序数据,分析RPN2基因的表达模式.对2016-2017年首都医科大学附属北京天坛医院收治的30例脑胶质瘤患者肿瘤样本采用实时荧光定量PCR验证RPN2基因的表达情况.根据RPN2基因的表达水平,将所有样本分为低表达组(154例)和高表达组(155例).以癌症基因组图谱数据库(TCGA)的mRNA测序数据和REMBRANDT的mRNA芯片数据作为独立验证数据集.采用方差分析和t检验分析RPN2基因的表达特征.应用Kaplan-Meier生存曲线、Log-rank检验以及Cox回归分析方法评价RPN2基因在脑胶质瘤患者预后评估中的作用.通过DAVID软件分析RPN2基因参与的GO生物学过程和KEGG信号通路.结果 CGGA mRNA测序数据显示,在世界卫生组织(WHO)Ⅱ、Ⅲ以及Ⅳ级脑胶质瘤中,RPN2的表达水平呈升高趋势(分别为-0.55±0.61、0.05±0.66以及0.36±1.20,P＜0.0001);实时荧光定量PCR也证实,RPN2的表达水平随胶质瘤WHO等级的升高呈逐渐升高的趋势.在TCGA脑胶质瘤的4个分型中,RPN2在神经元型中表达最低,在间质型中表达最高(分别为-0.80±0.56和0.68±1.02,P＜0.001).RPN2在IDH突变型脑胶质瘤中的表达低于其在野生型中的表达(分别为-0.22±0.77和0.22±1.18,P＜0.001).RPN2基因高表达组脑胶质瘤患者的总体生存期小于低表达组(P ＜0.001).RPN2基因的上述特征均在TCGA mRNA测序数据及REMBRANDT mRNA芯片数据集中得到类似的结果.多因素Cox分析显示,RPN2基因的表达水平是脑胶质瘤患者预后的独立预测因子(P=0.004).RPN2基因可能参与脑胶质瘤细胞的凋亡、分裂、增殖、黏附、血管生成等生物学过程.结论 RPN2基因与脑胶质瘤的恶性程度密切相关,可作为判断患者预后的指标及潜在的治疗靶点.

abstractsObjective To investigate the expression of ribophorin Ⅱ (RPN2) in gliomas and its relationship to clinical features and prognosis.Methods The clinical data and mRNA-seq data of 309 glioma samples were collected from Chinese Glioma Genome Atlas (CGGA) and the expression of RPN2 was retrospectively analyzed.The 30 glioma samples were collected by Beijing Tiantan Hospital Affiliated to Capital Medical University from 2016 to 2017.RT-qPCR was used to test RPN2 mRNA expression in those samples.TCGA mRNA sequencing and REMBRANDT mRNA array datasets were simultaneously used as validation datasets.The expression pattern of RPN2 in gliomas was analyzed by t-test and ANOVA.The relationship of RPN2 expression to the patient's overall survival was estimated by Kaplan-Meier method,logrank test and Cox regression analysis.The DAVID software was used to investigate the RPN2 functions in GO biological processes and KEGG pathways.Results In WHO Ⅱ,WHO Ⅲ and WHO Ⅳ gliomas,RPN2 expression was up-regulated along with glioma grade progression (-0.55 ± 0.61、0.05 ± 0.66 and 0.36 ±1.20,respectively,P ＜ 0.0001),which was further confirmed by RT-qPCR experiment.The expression of RPN2 was the lowest in neural subtype and highest in mesenchymal subtype (-0.80 ± 0.56 and 0.68 ±1.02,respectively,P ＜ 0.0001).RPN2 expression in IDH-mutant gliomas was significantly lower than that in IDH-wild gliomas (-0.22 ±0.77 and 0.22 ± 1.18,respectively,P ＜0.001).The overall survival of patients with high expression of RPN2 was significantly lower than that of patients with low expression (P ＜0.0001).Similar results were obtained in both TCGA mRNA-seq and REMBRANDT mRNA microarray datasets.Multi-variate Cox analysis showed that RPN2 expression was an independent predictor of prognosis (P =0.004).RPN2 might be related to the apoptosis,division,proliferation,adhesion and angiogenesis.Conclusion The expression of RPN2 seems to be associated with the malignant degree of gliomas and may be a prognostic marker and potential therapeutic target.