基于数据库挖掘分析TEAD2在胶质瘤诊断和治疗中的作用

Evaluating the role of TEAD2 in the diagnosis and therapy of glioma based on database mining

目的通过对数据库进行挖掘,分析转录增强缔合域(TEAD)蛋白⁃2(TEAD2)在胶质瘤中的表达水平及其与临床预后的关系。方法运用Timer2.0数据库、UCSC数据库和CCLE数据库分析TEAD2在泛癌中的表达水平。运用CGGA数据库和GBM线上数据库进行单细胞转录组测序数据分析。运用R语言对CGGA数据库和TCGA数据分析TEAD2与胶质瘤临床特征的关系。使用Kaplan⁃Meier进行生存分析,使用COX回归进行预后因素筛选。使用基因本体论(GO)分析和京都基因与基因组百科路径(KEGG)进行TEAD2相关基因功能富集。使用CCK8实验和细胞流式实验检测TEAD2小分子药物对胶质瘤细胞增殖和细胞周期的影响。结果TEAD2在多种肿瘤组织中表达水平升高。在胶质瘤中,TEAD2在肿瘤组织中高度富集,且主要在肿瘤细胞中表达。TEAD2与胶质瘤WHO临床病理分期、IDH突变状态和染色体1p/19q共缺失相关。高表达TEAD2的患者具有更差的预后,且TEAD2可以作为胶质瘤的独立预后因素。功能富集结果提示在胶质瘤中TEAD2可能参与肿瘤细胞的细胞周期、DNA复制等生物学过程。TEAD2小分子药物抑制胶质瘤细胞增殖,使细胞周期阻滞在G0/G1期。结论胶质瘤中TEAD2高表达,可以作为胶质瘤潜在的治疗和诊断靶点。

Objective The expression level of transcription⁃enhanced association domain protein⁃2(TEAD2)in glioma and its clinical significance were analyzed by mining the database.Methods Timer 2.0 database,UCSC database and CCLE database were used to analyze the expression level of TEAD2 in pan⁃cancer.Single⁃cell analysis was performed using the CGGA database and the GBM online database.The relationship between TEAD2 and the clinical characteristics of glioma was analyzed by using R in the CGGA database and TCGA database.Kaplan⁃Meier was used for survival analysis and COX regression was used for prognostic factor screening.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes pathways(KEGG)were used for functional enrichment of TEAD2⁃related genes.CCK8 assay and flow cytometry were used to investigate the effects of TEAD2 small molecule drugs on the prolif⁃eration and cell cycle of glioma cells.Results The expression level of TEAD2 was increased in various tumor tissues.In glioma,TEAD2 was highly enriched in tumor tissues and mainly expressed in tumor cells.TEAD2 was correlated with glioma WHO clinicopathological stage,IDH mutation status,and chromo⁃some 1p/19q co⁃deletion.Patients with high expression of TEAD2 had worse prognosis,and TEAD2 could be used as an independent prognostic factor for glioma.Functional enrichment results suggested that TEAD2 might be involved in the cell cycle,DNA replication in glioma.TEAD2 small molecule drugs inhibited the proliferation of glioma cells and caused cell cycle arrest in the G0/G1 phase.Conclusion TEAD2 is highly expressed in glioma and can be used as a potential therapeutic and diagnostic target for glioma.