摘要
目的探讨同源盒基因B2(HOXB2)在脑胶质瘤中的表达及其临床意义。方法采用生物信息学分析方法分析中国脑胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库中1 001例脑胶质瘤患者的转录组信息及临床资料。采用Kaplan-Meier分析法探究HOXB2对患者生存期的影响;单因素和多因素Cox回归分析法分析HOXB2表达对脑胶质瘤患者预后的影响。Pearson相关分析法筛选与HOXB2相关的基因,通过基因本体分析(GO)、京都基因和基因组百科全书(KEGG)对这些基因进行功能富集分析。结果 CGGA和TCGA数据库中,HOXB2在世界卫生组织(WHO)分级Ⅱ级、Ⅲ级和Ⅳ级脑胶质瘤中的表达差异均有统计学意义(均P<0.05),肿瘤的级别越高,HOXB2的表达水平越高;HOXB2高表达组的脑胶质瘤患者的总体生存时间均低于低表达组(均P<0.01)。多因素Cox回归分析结果显示,CGGA数据库中,HOXB2高表达(HR=1.237,95%CI:1.094~1.398,P<0.001)、肿瘤级别(WHO Ⅳ级)(HR=3.447,95%CI:2.456~4.837,P<0.001)为脑胶质瘤患者生存的独立影响因素;TCGA数据库中,HOXB2高表达(HR=1.580,95%CI:1.320~1.892,P<0.001)、年龄(HR=1.037,95%CI:1.027~1.048,P<0.001)、肿瘤级别(WHO Ⅳ级)(HR=2.500,95%CI:1.782~3.505,P<0.001)和IDH1突变(HR=0.509,95%CI:0.360~0.719,P<0.001)为脑胶质瘤患者生存的独立影响因素。GO和KEGG分析结果显示,HOXB2与细胞外基质、免疫反应、炎性反应等通路密切相关,其表达水平与多种基质金属蛋白酶呈明显的正相关(均P<0.05)。结论在脑胶质瘤组织中,随着肿瘤级别的升高,HOXB2的表达水平也逐渐升高,可作为脑胶质瘤患者预后的预测因素。
Objective To explore the expression,clinical significance and biological function of HOXB2 in gliomas.Methods Bioinformatics analysis was employed to retrospectively analyze the transcriptome and information clinical data of 1001 glioma patients in the Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA).Kaplan-Meier(KM)analysis was used to explore the effect of HOXB2 on the survival of patients.Univariate and multivariate Cox regression analysis methods were used to evaluate the effect of HOXB2 on the prognosis of glioma patients.Pearson correlation analysis was used to screen genes related to HOXB2,and gene enrichment analysis was performed on those genes through Gene Ontology analysis(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).Results The expression levels of HOXB2 in gradeⅡ,gradeⅢand gradeⅣgliomas were significantly different(all P<0.05).Higher tumor grade was associated with higher expression of HOXB2.The overall survival time of glioma patients in the HOXB2 high expression group was significantly lower than that in the HOXB2 low expression group(P<0.01).CGGA data showed that the expression of HOXB2(HR=1.237,95%CI:1.094-1.398,P<0.001)and tumor grade(WHO gradeⅣ)(HR=3.447,95%CI:2.456-4.837,P<0.001)were independent prognostic factors.TCGA data showed that HOXB2 expression(HR=1.580,95%CI:1.320-1.892,P<0.001),age(HR=1.037,95%CI:1.027-1.048,P<0.001),tumor grade(WHO gradeⅣ)(HR=2.500,95%CI:1.782-3.505,P<0.001)and IDH1 mutation status(HR=0.509,95%CI:0.360-0.719,P<0.001)were independent prognostic factors.The results as above suggested that the expression of HOXB2 was negatively correlated with overall survival in glioma patients.GO and KEGG analysis revealed that the expression of HOXB2 was closely related to extracellular matrix,antigen presentation,inflammation and other pathways.Matrix metalloproteinases(MMPs)showed a significant positive correlation with the expression of HOXB2,suggesting that HOXB2 promoted the invasion of gliomas(all P<0.05).Conclusion The expression of HOBX2 is associated with tumor grade which could be used as an independent prognostic indicator in patients with gliomas.
作者
潘鑫
刘伟
王晓文
胡历博
柴毅
王俊华
张玉琪
Pan Xin;Liu Wei;Wang Xiaowen;Hu Libo;Chai Yi;Wang Junhua;Zhang Yuqi(Department of Neurosurgery,Tsinghua University Yuquan Hospital,Beijing 100040,China;School of Clinical Medicine,Tsinghua University,Beijing 100084,China)
出处
《中华神经外科杂志》
CSCD
北大核心
2020年第9期957-961,共5页
Chinese Journal of Neurosurgery
基金
国家自然科学基金(81071885)。
