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目的:分析染色体结构维持蛋白4(n SMC4)基因在脑胶质瘤中的表达情况及其临床意义。n 方法:(1)下载中国脑胶质瘤基因组图谱计划(CGGA)数据库中749例胶质瘤组织的n SMC4 mRNA表达数据及其患者的临床资料。采用单因素和多因素Cox回归分析明确胶质瘤患者预后不良的独立影响因素。绘制并比较n SMC4 mRNA高表达组、n SMC4 mRNA低表达组患者的生存曲线。采用受试者工作特征(ROC)曲线分析n SMC4 mRNA对患者1、3、5年生存率的预测效能。(2)使用基因表达谱数据动态分析(GEPIA)评价癌症基因组图谱(TCGA)数据库中胶质瘤组织的n SMC4 mRNA表达水平与其患者总生存率的关系。通过人类蛋白质图谱(HPA)在线数据库测定高级别胶质瘤(胶质母细胞瘤)、低级别胶质瘤中SMC4蛋白的表达。(3)基因组富集分析比较n SMC4 mRNA高表达组、n SMC4 mRNA低表达组胶质瘤间基因本体(GO)和京都基因与基因组百科全书(KEGG)通路的差异。采用基因共表达分析与n SMC4 mRNA存在相关关系的基因。n 结果:(1)多因素Cox回归分析显示n SMC4 mRNA(n HR=1.314，n 95%CI：1.209~1.428，n P=0.000)、原发-复发-继发(PRS)类型、WHO分级、年龄、化疗、异柠檬酸脱氢酶(n IDH)突变和染色体1p/19q缺失是胶质瘤患者预后不良的独立影响因素。生存分析显示n SMC4 mRNA低表达组患者的总生存率高于n SMC4 mRNA高表达组，差异有统计学意义(n P<0.05)。ROC曲线分析显示，n SMC4 mRNA预测患者1年、3年和5年生存率的曲线下面积(AUC)分别为0.712、0.784、0.791。(2)低级别、高级别胶质瘤中n SMC4 mRNA表达水平均高于正常对照脑组织，差异均有统计学意义(n P<0.05)。低级别胶质瘤中n SMC4 mRNA低表达组患者的总生存率高于n SMC4 mRNA高表达组，差异有统计学意义(n P0.05)。低级别胶质瘤组织中SMC4蛋白表达显著低于高级别胶质瘤。(3)基因组富集分析显示n SMC4 mRNA高表达组胶质瘤中富集的GO是凝聚核染色体、驱动蛋白复合体、减数分裂细胞周期、减数分裂细胞周期过程；富集的KEGG通路包括细胞周期、DNA复制、错配修复、P53信号通路、胰腺癌等相关通路。基因共表达分析显示与SMC4 mRNA表达呈正相关关系的前5个基因为苯并咪唑出芽抑制解除同源物蛋白1(BUB1)、丝氨酸/苏氨酸蛋白激酶1(WEE1)、着丝粒蛋白L(CENPL)、驱动蛋白超家族23(KIF23)、Shugoshin样蛋白2(SGOL2)，与n SMC4 mRNA表达呈负相关关系的前5个基因为F框/WD40域蛋白4(FBXW4)、副肿瘤样抗原-L2(PNMAL2)、成熟酶蛋白K(MATK)、PASL10A、长链编码基因CTD-2210P24.4。n 结论:SMC4 mRNA表达水平较高的胶质瘤患者预后较差，n SMC4 mRNA为高危因素，可作为胶质瘤患者的独立预后指标，其生物学功能与胶质瘤的DNA复制相关。n “,”Objective:To analyze the expression of structural maintenance of chromosome 4(n SMC4) gene in glioma and its clinical significance.n Methods:(1) The n SMC4 mRNA expression data of 749 glioma tissues and clinical data of these glioma patients were downloaded from Chinese Glioma genome Atlas (CGGA) database. Univariate Cox analysis and multivariate Cox analysis were used to analyze the independent influencing factors for poor prognosis in patients with glioma. Patients were divided into high n SMC4 mRNA expression group and low n SMC4 mRNA expression group; Kaplan-Meier method was used to draw the survival curve of these patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of n SMC4 mRNA in 1-, 3- and 5-year survival of these patients. (2) The relationships between n SMC4 mRNA expression levels in glioma tissues from cancer Genome Atlas (TCGA) database and overall survival of these glioma patients were analyzed by gene expression profiling interactive analysis (GEPIA). The SMC4 protein expressions in high-grade glioma (glioblastoma) and low-grade glioma were determined by human protein atlas (HPA) online database. (3) Genomic enrichment analysis was used to analyze and compare the differences of gene body (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in gliomas between n SMC4 mRNA high expression group and SMC4 mRNA low expression group. Co-expression analysis was performed to analyze the genes related to n SMC4 mRNA.n Results:(1) Multivariate Cox analysis showed that n SMC4 mRNA (n HR=1.314, n 95%CI: 1.209-1.428, n P=0.000), glioma primary-recurrent-secondary (PRS) type, glioma WHO grading, age, chemotherapy, isocitrate dehydrogenase (n IDH) mutation and 1P/19q deletion were independent influencing factors for poor prognosis of glioma patients. Survival analysis showed that the overall survival of patients with low n SMC4 mRNA expression was significantly higher than that of patients with high n SMC4 mRNA expression (n P<0.05). The area under the curve (AUC) of ROC was 0.712, 0.784 and 0.791, respectively, in predicting 1-year survival rate, 3-year survival rate and 5-year survival rate. (2)n SMC4 mRNA expressions in low-grade and high-grade gliomas were statistically lower than those in normal control brain tissue (n P<0.05). The overall survival of low-grade glioma patients with lown SMC4 mRNA expression was significantly higher than that of patients with n SMC4 mRNA high expression (n P0.05). The SMC4 protein expression in low-grade glioma was significantly higher than that in high-grade glioma. (3) Genome enrichment analysis showed that GO enriched in gliomas with highn SMC4 mRNA expression was about nuclear chromosome aggregation, protein complex driving, cell cycle meiotic and process of meiotic cell cycle. KEGG enrichment included cell cycle, DNA replication, mismatch repair, P53 signaling pathway, pancreatic cancer and other related pathways. Gene co-expression analysis showed that the first 5 genes, including n BUB1, n WEE1, n CENPL, n KIF23 and n SGOL2, were positively correlated with n SMC4 mRNA expression; and the first 5 genes, including n FBXW4, n PNMAL2, n MATK, n PASL10A and n CTD-2210P24.4, were negatively correlated with n SMC4 mRNA expression.n Conclusions:Glioma patients with n SMC4 mRNA high expression have poor prognosis. As a high risk factor, n SMC4 mRNA can be used as an independent prognostic indicator of glioma patients, and its biological function is related to DNA replication of glioma.n