基于数据库数据分析脑胶质瘤组织中FN1基因的表达变化及其预后预测效能

FN1 gene expression and its prognostic efficiency in glioma based on database data

目的 观察纤维连接蛋白1(FN1)基因在胶质瘤组织中的表达变化,并探讨其与患者临床病理特征和预后的相关性。方法 基于TCGA数据库和GTEx数据库中胶质瘤及正常脑组织转录组数据,分析FN1基因在胶质瘤与正常脑组织中的表达差异及与患者临床病理特征的相关性。用Kaplan-Meier生存分析及ROC分析FN1基因在胶质瘤患者预后中的价值。使用ssGSEA算法及TIMER数据库进行肿瘤免疫细胞浸润分析。利用clusterProfiler包进行KEGG通路及GO功能富集分析。通过STRING数据库得到FN1蛋白互作网络。利用cancerSEA数据库进行FN1基因表达与肿瘤细胞功能状态的相关性分析。结果 FN1基因在胶质瘤组织中表达明显上调(P<0.01),并与肿瘤分级增加、IDH分型、1p19q缺失、年龄以及胶质瘤的组织病理学分型有关(P均<0.001)。FN1基因高表达是胶质瘤患者的不良预后因素。FN1基因表达与肿瘤微环境中B细胞、CD4^(+)T细胞、CD8^(+)T细胞、树突状细胞、中性粒细胞、巨噬细胞等免疫细胞免疫浸润有关(P均<0.001)。FN1基因表达与肿瘤血管内皮细胞增生、肿瘤细胞分化呈正相关(r分别为0.58、0.47,P均<0.001),与肿瘤细胞DNA损伤、细胞周期呈负相关(r分别为-0.52、-0.45,P均<0.01)。FN1基因有关的生物过程共有351条,包括补体激活等;细胞组分共有28条,包括免疫球蛋白复合物等;分子功能共有94条,包括抗原结合等。KEGG分子信号通路29条,主要包括细胞因子-细胞因子受体相互作用等。FN1的互作蛋白主要有ITGB1、ITGB3、ITGA3等。结论 FN1基因在胶质瘤组织中的表达上调,是预后不良的指标;与肿瘤免疫细胞浸润及胶质瘤细胞功能状态相关;FN1基因有关的生物功能与补体激活、免疫球蛋白复合物、抗原结合等有关,参与的信号通路要包括细胞因子-细胞因子受体相互作用等,互作蛋白主要有ITGB等。

Objective To observe the expression changes of fibronectin1(FN1)gene in glioma tissues and to investigate its correlations with clinicopathological features and prognosis of patients.Methods Based on the transcriptome data of gliomas and normal brain tissues in TCGA database and GTEx database,the difference of FN1 gene expression between gliomas and normal brain tissues and the correlation between FN1 gene expression and clinicopathological characteristics were analyzed.Kaplan-Meier survival analysis and ROC curve analysis were used to evaluate the prognostic value of FN1 gene in patients with glioma.Tumor immune cell infiltration was analyzed by ssGSEA algorithm and TIMER database.ClusterProfiler package was used to analyze KEGG pathway and GO functional enrichment.The FN1 protein interaction network was obtained by STRING database.The correlation between FN1 gene expression and tumor cell function was analyzed by cancerSEA database.Results FN1 gene was significantly up-regulated in gliomas(P<0.01).The high expression of FN1 gene was related to increased tumor grade,IDH classification,1p19q deletion,age and histopathological classification of glioma(all P<0.001).High expression of FN1 gene was a poor prognostic factor for patients with glioma.FN1 gene expression was associated with B cells,CD4^(+)T cells,CD8+T cells,dendritic cells,neutrophils,macrophages and other immune cells immune infiltration in tumor microenvironment(all P<0.001).The expression of FN1 gene was positively correlated with proliferation of tumor vascular endothelial cells and tumor cell differentiation(r=0.58,r=0.47;all P<0.001),and was negatively correlated with tumor cell DNA damage and cell cycle(r=-0.52,r=-0.45;P<0.001,P<0.01).There were 351 biological processes related to FN1 gene(BP),including complement activation,28 cellular components(CC),including immunoglobulin complexes,and 94 molecular functions(MF),including antigen binding,etc.There were 29 KEGG molecular signaling pathways,mainly including cytokine-cytokine receptor interaction.The main interacting proteins of FN1 were ITGB1,ITGB3,ITGA3 and so on.Conclusions The expression of FN1 gene in glioma tissues was up-regulated,which was an indicator of poor prognosis;it was related to tumor immune cell infiltration and glioma cell function;the biological function of FN1 gene was related to complement activation,immunoglobulin complex,antigen binding and so on;cytokine-cytokine receptor interactions were involved in signal pathways,and the main interaction proteins were ITGB and so on.