N-myc下游调节基因3低表达与胶质瘤患者预后不良和免疫浸润的相关性研究  

Correlation between low expression of N-myc downstream regulatory gene 3 and poor prognosis and immune infiltration in patients with glioma

作　　者：刘晓鹏[1] 陈美琴 台立稳[2] 孙玉晨[1] 王苑宇[1] 杜浩阳 宋燕飞 王建格 董田玉 Liu Xiaopeng;Chen Meiqin;Tai Liwen;Sun Yuchen;Wang Yuanyu;Du Haoyang;Song Yanfei;Wang Jiange;Dong Tianyu(Department of Neurosurgery,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院神经外科,石家庄050000 [2]河北医科大学第二医院神经内科,石家庄050000 [3]河北医科大学解剖教研室 [4]邢台市临城县人民医院神经外科

出　　处：《脑与神经疾病杂志》2022年第10期610-616,共7页Journal of Brain and Nervous Diseases

摘　　要：目的探讨胶质瘤中N-myc下游调节基因3 (N-myc downstream-regulated gene 3,NDRG3)与免疫浸润和预后价值的关系。方法 首先本文通过Gliovis、Human Protein Atlas等工具分析了NDRG3在胶质瘤的不同数据库中表达量及其与胶质瘤级别的差异。进一步通过将NDRG3的中位表达量分为高低两组,研究其在Gliovis中CGGA (Chinese GliomaGenome Atlas)、TCGA (Cancer Genome Atlas)、Rembrandt、Phillips和Gravendeel数据库中的对胶质瘤生存预后的影响并绘制了各数据库的NDRG3风险系数森林图。随后依据CGGA数据库,本文研究了胶质瘤级别、年龄、性别、复发、IDH程度和1p19q共表达缺失等临床特征与NDRG3表达量之间的关系,通过多因素COX回归分析影响胶质瘤患者预后的独立因素。依托GEPIA和STRING数据库,探索了NDRG3的相关蛋白并进行GO和KEGG富集分析,通过R语言分析绘制了TCGA胶质瘤数据库中NDRG3基因正负相关的多通路富集图,为后续NDRG3的作用机制及通路分析提供了有力支持。最后本文通过CiberSort算法和TIMER2.0网络数据库研究了NDRG3与胶质瘤免疫浸润的关系。结果 在胶质瘤中,NDRG3的表达随着肿瘤级别的增高,表达量显著降低(P<0.05)。NDRG3表达较低的患者,总体生存率(OS)显著低于高表达组(P<0.05)。CGGA多因素COX回归分析中显示,年龄、等级、NDRG3表达量、PRS类型、是否化疗、IDH是否变异和1p19q编码状态为影响胶质瘤患者预后的独立因素(P<0.05)。GO富集分析数据表明,NDRG3相关基因与突触相关的生物过程等相关。KEGG富集分析显示,NDRG3可能通过“MAPK信号通路”和“Ras信号通路”参与对肿瘤发病机制的影响。TCGA样本中GSEA (gene set enrichment analysis)分析显示NDRG3低表达组显著性富集在KEGG_AUTOIMMUNE_THYROID_DISEASEKEGG_INTESTINAL_IMMUNE_NETWORK_FOR_IGA_PRODUCTION、KEGG_PRIMARY_IMMUNODEFICIENCY等免疫通路中。Tregs、NK激活细胞、Monocytes、MacrophagesM2四种细胞�Objective To investigate the relationship between the N-myc downstream regulated gene 3(NDRG3) and immune infiltration and prognostic value in gliomas.Methods Firstly,we analyzed the expression of NDRG3 in different databases of glioma and its difference with glioma grade by tools such as Gliovis and Human Protein Atlas.Next,the median expression of NDRG3 was divided into high and low groups,and its effect on survival prognosis of glioma in CGGA(Chinese GliomaGenome Atlas),TCGA(The Cancer Genome Atlas),Rembrandt,Phillips and Gravendeel databases in Gliovis was investigated and forest plots of NDRG3 risk coefficients were drawn for each database.Subsequently,based on the CGGA database,we investigated the relationship between clinical characteristics such as glioma grade,age,gender,recurrence,degree of IDH and 1 p19 q co-expression deficiency and NDRG3 expression,and analyzed independent factors affecting the prognosis of glioma patients by multifactorial COX regression.Relying on GEPIA and STRING databases,we explored NDRG3-related proteins and performed GO and KEGG enrichment analysis,and mapped the positive and negative NDRG3 gene related multiple pathway enrichment in TCGA glioma database by R language analysis,which provided strong support for the subsequent NDRG3 mechanism of action and pathway analysis.Finally,we investigated the relationship between NDRG3 and glioma immune infiltration by using the CiberSort algorithm and the TIMER2.0 network database.Results In glioma,NDRG3 expression significantly decreased with increasing tumor grade(P<0.05).patients with lower NDRG3 expression had significantly lower overall survival(OS) than the high expression group(P<0.05).In CGGA multifactorial cox regression analysis,age,grade,NDRG3 expression,PRS type,whether chemotherapy was given,whether IDH variant and 1 p19 q coding status were independent factors affecting the prognosis of glioma patients(P<0.05).The GO enrichment data showed that NDRG3-related genes are associated with synapse-related biological processes,et

关 键 词：N-MYC下游调节基因 胶质瘤 预后价值 免疫浸润 

分 类 号：R739.4[医药卫生—肿瘤]