首页|原发性胶质母细胞瘤瘤内细菌特征基因及其功能研究

原发性胶质母细胞瘤瘤内细菌特征基因及其功能研究

扫码查看
目的 分析原发性胶质母细胞瘤(GBM)患者肿瘤组织中细菌相关特征基因,并研究肿瘤内细菌相关特征基因在GBM中的功能及作用机制.方法 采用基于癌症基因组图谱(TCGA)数据分析得到的原发性GBM瘤内细菌相关特征基因的公开数据,共152例.根据GBM患者总生存时间的中位数,将其分为低生存组(78例)和高生存组(74例).使用秩和检验评估组间α多样性的差异;采用非度量多维尺度(NMDS)分析和主坐标分析(PCoA)评估组间β多样性的差异;采用线性判别分析(LDA)比较两组GBM样本中丰富度存在显著差异的细菌种类.分别根据各差异细菌相关特征基因的相对丰富度将152例患者分为高丰富度组和低丰富度组,采用Kaplan-Meier法分析高丰富度组与低丰富度组患者生存率的差异.对与良好预后相关的高丰富度细菌相关特征基因GBM样本中显著上调的基因进行基因本体论(GO)生物过程功能注释和京都基因和基因组百科全书(KEGG)通路富集分析;通过TCGA转录组测序数据集分析肿瘤免疫微环境景观,应用曼特尔检验分析免疫细胞浸润含量与预后相关细菌特征基因的相关性.所有数据分析均采用R软件,以P<0.05为差异有统计学意义.结果 152例GBM组织中共鉴定出252种细菌相关特征基因,其中234种特征基因在低生存组与高生存组均存在,8种仅存在于低生存组,10种仅存在于高生存组.NMDS和PCoA结果显示,两组的β多样性的差异有统计学意义(P<0.05).LDA显示,高生存组与低生存组的肿瘤组织中细菌相关特征基因的丰富度存在差异(P<0.05),其中脆弱拟杆菌相关特征基因在高生存组的丰富度较高(P<0.05),并与患者的总生存期呈正相关(x2=4.13,P<0.05).功能富集分析显示,肿瘤内脆弱拟杆菌相关特征基因丰富度较高的患者肿瘤组织中高表达与免疫途径相关的基因(P<0.05).曼特尔检验分析结果显示,原发性GBM肿瘤组织中脆弱拟杆菌相关特征基因的丰富度与M1巨噬细胞浸润呈正相关(P<0.05).结论 脆弱拟杆菌相关特征基因在高生存原发性GBM患者肿瘤组织中的丰富度较高,并影响肿瘤的免疫微环境.
The bacterial characteristic genes and their functions in primary glioblastomas
Objective To analyze the bacteria composition in primary tumor tissues of patients with glioblastomas(GBM)and to study the function and mechanism of intratumoral bacteria-related characteristic genes in GBM.Methods A total of 152 cases of primary GBM were analyzed based on the public data of bacteria-related genes within tumors based on The Cancer Genome Atlas(TCGA).According to the median overall survival time of GBM patients,they were divided into a low survival group(78 cases)and a high survival group(74 cases).Differences in α diversity between groups were evaluated using rank sum tests.Non-metric multidimensional scaling(NMDS)analysis and principal co-ordinates analysis(PCoA)were used to assess the differences in β diversity between groups.Linear discriminant analysis(LDA)was used to compare bacteria-related characteristic genes in two groups of GBM samples.According to the relative abundance of different bacteria-related characteristic genes,152 patients were divided into high abundance group and low abundance group.Kaplan-Meier method was used to analyze the difference in survival rate between the high abundance group and the low abundance group.Gene ontology(GO)functional annotation of biological processes and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for significantly upregulated genes in high-abundance bacterial-related characteristic gene samples associated with better prognosis.Tumor immune microenvironment landscape was analyzed by TCGA transcriptome sequencing data set,and the correlation between immune cell infiltration content and prognostic related bacterial characteristic genes was analyzed by Mantel test.All data were analyzed using R software,and P<0.05 was considered statistically significant.Results A total of 252 bacteria-related characteristic genes were identified in 152 GBM tissues,of which 234 were present in both the low survival group and the high survival group,8 were present only in the low survival group and 10 were present only in the high survival group.NMDS and PCoA analyses showed significant statistical differences in β diversity between the two groups.LDA analysis showed that bacteria-related characteristic genes in tumor tissues was different between the high survival group and the low survival group(P<0.05).The abundance of Bacteroides fragile-related characteristic genes was higher in the high survival group(P<0.05),and was positively correlated with the overall survival of patients(x2=4.13,P<0.05).Functional enrichment analysis showed that genes related to immune pathway were highly expressed in tumor tissues of patients with higher abundance of Bacteroides fragilis-related characteristic genes(P<0.05).Mantel test analysis results showed that the abundance of Bacteroides fragilis-related characteristic genes in primary GBM tumor tissues was positively correlated with M1 macrophage infiltration(P<0.05).Conclusion Bacteroides_fragilis-related characteristic genes are more abundant in primary tumors from high survival GBM patients and impact the tumor immune microenvironment.

GlioblastomaBacteria related geneIntratumoral bacteriTranscriptome

于润泽、魏成、王博、李泽生、靖博元、韩磊

展开 >

天津医科大学总医院,天津市神经病学研究所,教育部"中枢神经损伤与再生"重点实验室,天津市"神经损伤变异与再生"重点实验室,天津 300052

胶质母细胞瘤 细菌相关特征基因 肿瘤内细菌 转录组

国家自然科学基金天津市卫生健康科技项目重点项目

81773187TJWJ2023ZD001

2024

中华神经外科杂志
中华医学会

中华神经外科杂志

CSTPCD北大核心
影响因子:1.107
ISSN:1001-2346
年,卷(期):2024.40(9)