FSTL1基因在胶质瘤发展中作用的研究

Study of the role of the FSTL1 gene in glioma development

目的采用生物信息学分析FSTL1基因在胶质瘤发展中的潜在作用。方法从中国胶质瘤基因组图谱计划(CGGA)数据库中下载胶质瘤基因表达量及临床数据,按照FSTL1表达水平将胶质瘤患者分为高表达组(FSTL1表达量≥29.1 reads)和低表达组(FSTL1表达量<29.1 reads)。寻找高低组间差异基因进行基因本体论(GO)分析和基因集富集分析(GSEA)。采用最小绝对收缩和选择算法分析构建预后模型,并在胶质瘤纵向分析(GLASS)数据集中进行验证。结果FSTL1的高表达与较差的临床特征有关,如:1p19q的非联合缺失、IDH野生型、较高的WHO级别等。低表达组患者的预后均明显优于高表达组患者,差异有统计学意义(P<0.05)。GO分析结果显示,差异基因主要集中在细胞外基质组织、免疫相关、脉管系统发育等。基因富集分析发现的通路主要有:ECM_RECEPTOR_INTERACTION、G2M_CHECKPOINT、L6_JAK_STAT3_SIGNALING、TNFA_SIGNALING_VIA_NFKB等。与低表达组相比,高表达组显示出较高的免疫和基质评分,但纯度评分较低(均P<0.001),构建风险评分的基因有:ALDOC、GLC1、LINC00634、TGIF1、TPM4、TRAM2。Kaplan-Meier生存曲线显示高风险评分的胶质瘤患者的预后较差。构建生存预测诺模图,受试者工作特征、校正曲线均显示该模型有较好的预测能力。结论FSTL1与胶质瘤的临床和分子特征有关,FSTL1的表达量与肿瘤恶性程度有关,是胶质瘤患者的潜在治疗靶点和独立的预后因素。

Objective Utilizing bioinformatics analysis to investigate the potential role of the FSTL1 gene in the development of gliomas.Methods The glioma gene expression levels and clinical data were downloaded from the Chinese Glioma Genome Atlas Project(CGGA)database.Glioma patients were categorized into high expression group(FSTL1 expression level≥29.1 reads)and low expression group(FSTL1 expression level<29.1 reads)based on FSTL1 expression level.Differential gene analysis was conducted between the high and low expression groups,and perform gene ontology(GO)and gene set enrichment analysis(GSEA).The least absolute shrinkage and selection operator(LASSO)algorithm was applied to construct a prognostic model.It was also verified in the Glioma Longitudinal Analysis(GLASS)dataset.Results High expression of FSTL1 is associated with poor clinical features,such as non-codelof 1p19q,IDH wildtype,higher grade(WHOⅢ-Ⅳ),etc.The prognosis of patients in the low expression group was significantly better than that in the high expression group,and the difference was statistically significant(P<0.05).GO analysis showed that DEGs is mainly concentrated in extracellular matrix tissue,immune-related,vascular system development,etc.The main pathways identified by gene enrichment analysis(GSEA)were:ECM_RECEPTOR_INTERACTION,G2M_CHECKPOINT,L6_JAK_STAT3_SIGNALING,and TNFA_SIGNALING_VIA_NFKB,etc.Compared with the low expression group,the high expression group showed higher immune and matrix scores,but lower purity scores(all P<0.001).Genes used for constructing the risk score were:ALDOC,GLC1,LINC00634,TGIF1,TPM4,and TRAM2.The Kaplan-Meier survival curve showed a poor prognosis of the high-risk score.Construct a survival prediction nomogram,and the subject operating characteristics and the correction curve all showed that the model had a good predictive ability.Conclusion FSTL1 is related to the clinical and molecular characteristics of glioma,and its expression is related to the degree of tumor malignancy,being a potential therapeutic target and an independent prognostic factor in glioma patients.