摘要
目的探讨同源盒基因D3(HOXD3)在胶质瘤中的表达及其生物学功能。方法回顾性收集中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)中1001例胶质瘤患者的临床资料及转录组数据,采用单因素方差分析比较不同病理分级胶质瘤间HOXD3表达水平的差异;并根据HOXD3表达水平的均值,分别将CGGA和TCGA数据库中的患者分为HOXD3低表达组与HOXD3高表达组,采用Kaplan-Meier生存分析比较HOXD3高表达组与HOXD3低表达组间生存期的差异,采用单因素回归分析及多因素Cox回归分析明确HOXD3对胶质瘤患者预后的影响;最后通过基因本体(GO)分析、京都基因和基因组百科全书(KEGG)分析以及基因富集分析(GSEA)探究HOXD3可能参与的信号通路,并采用Pearson相关分析法分析HOXD3与其他基因表达的相关性。结果(1)HOXD3的表达水平随着胶质瘤病理分级的升高逐渐升高(CGGA数据中Ⅱ、Ⅲ、Ⅳ级胶质瘤的表达水平分别为0.737±0.085、1.323±0.125、1.652±0.083;TCGA数据中Ⅱ、Ⅲ、Ⅳ级胶质瘤的表达水平分别为0.082±0.008、0.177±0.014、0.259±0.016),不同病理分级间HOXD3表达水平差异均有统计学意义(P<0.05)。(2)与HOXD3低表达组相比,HOXD3高表达组患者的生存期明显缩短,差异有统计学意义(P<0.05)。CGGA数据显示HOXD3表达水平(HR=1.348,95%CI:1.171~1.552,P=0.000)、肿瘤病理分级和异柠檬酸脱氢酶1(IDH1)突变状态为胶质瘤患者预后的独立影响因素;TCGA数据显示HOXD3表达水平(HR=2.147,95%CI:1.252~3.681,P=0.005)、年龄、肿瘤病理分级和IDH1突变状态为胶质瘤患者预后的独立影响因素。(3)GO分析、KEGG分析和GSEA结果均提示HOXD3参与细胞周期的调控;Pearson相关分析发现HOXD3的表达水平与多种细胞周期调控基因的表达水平呈明显正相关关系(P<0.05)。结论HOXD3为胶质瘤预后的独立影响因素,其生物学功能与胶质瘤细胞的周期调控相关。
Objective To investigate the clinical significance of homeobox gene D3(HOXD3)expression in glioma and its biological functions.Methods A total of 1001 patients with glioma collected from Chinese Glioma Genome Atlas(CGGA)and the Cancer Genome Atlas(TCGA)were chosen in our study;their clinical data and transcriptome data were retrospectively analyzed.One-way analysis of variance was used to evaluate the differences of HOXD3 expressions in different pathological grading of glioma.These patients were divided into HOXD3 low expression group and HOXD3 high expression group according to the average value of HOXD3 expression.Kaplan-Meier survival analysis was used to compare the differences in survival time between patients from the HOXD3 high-expression group and HOXD3 low-expression group.Univariate and multivariate Cox regression analyses were used to investigate the effect of HOXD3 on the prognoses of patients with glioma.Gene ontology(GO)analysis,Kyoto encyclopedia of genes and genomes(KEGG)and gene set enrichment analysis(GSEA)were used to investigate the biological function of HOXD3.Pearson correlation analysis was used to analyze the correlation between HOXD3 expression and expressions of other genes.Results(1)The expression level of HOXD3 gradually increased with the increase of pathological grading of glioma(in the CGGA data,the expression levels in grading II,III and IV gliomas were 0.737±0.085,1.323±0.125 and 1.652±0.083,respectively;in TCGA data,the expression levels in grading II,III and IV gliomas were 0.082±0.008,0.177±0.014 and 0.259±0.016,respectively).The HOXD3 expression levels among different pathological grading of glioma were statistical different(P<0.05).(2)As compared with that in the HOXD3 low-expression group,the survival time of patients in the HOXD3 high-expression group was significantly shorter(P<0.05).CGGA data showed that the HOXD3 expression(HR=1.348,95%CI:1.171-1.552,P=0.000),tumor grading(HR=2.793,95%CI:1.981-3.936,P=0.000)and isocitrate dehydrogenase 1(IDH1)mutation status(HR=0.689,95%CI:0.492-0.964,P=0.029)were independent influencing factors for prognoses of glioma patients.TCGA data showed that the HOXD3 expression(HR=2.147,95%CI:1.252-3.681,P=0.005),age(HR=1.036,95%CI:1.026-1.046,P=0.000),tumor grading(HR=3.178,95%CI:2.299-4.392,P=0.000)and IDH1 mutation status(HR=0.440,95%CI:0.317-0.613,P=0.000)were independent influencing factors for prognoses of glioma patients.(3)GO,KEGG and GSEA analyses showed that HOXD3 was closely related to the cell cycle;the HOXD3 expression was positively correlated with various cell cycle associated genes(P<0.05).Conclusion HOXD3 is an independent influencing factor for prognoses of glioma patients,whose biological function is related to the periodic regulation of glioma.
作者
赵亚鹏
王艳敏
张振宇
刘献志
Zhao Yapen;Wang Yanmin;Zhang Zhenyu;Liu Xianzhi(Department of Neurosurgery,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2020年第10期988-994,共7页
Chinese Journal of Neuromedicine
基金
国家自然科学基金(81702465、U1804172)。
