基于转录组数据筛选胸腺瘤致病基因及调控通路
To Screen Thymoma Pathogenic Genes and Regulatory Pathways Based on Transcriptome Data

目的：综合生物信息学分析，探究胸腺瘤的致病基因及调控通路。方法：GEO基因表达总数据库检索并下载3组胸腺瘤基因芯片数据，并利用GEO2R筛选出差异基因(DEGs)，然后通过Metascape和STRING在线软件对差异基因进行GO、KEGG富集分析和蛋白互作网络构建；然后应用Cytoscape软件筛选致病基因；最后应用UALCAN和GEPIA数据库对关键基因进行验证、生存分析及调控机制通路探究。结果：分析三组数据集获得1259个共同DEGs，GO、KEGG富集分析和SinoBiological网站检索显示DEGs参与肿瘤坏死因子信号通路、跨膜受体蛋白酪氨酸激酶信号通路、TNF信号通路、PI3K-Akt信号通路、鞘脂类信号通路、Hippo信号通路、钙信号通路、癌症通路、癌症中的转录失调和造血细胞系。30个关键致病基因，包括ITGA4、ITGB3、ITGB5、ITGB6、ITGA8、ITGA11、COL6A1、THBS2、COL6A2等。通过对致病基因进行验证、通路探究和生存分析，发现ITGA4、CD4、THY1、CD1D和IL2RB均可影响患者总体生存率，提示可作为THY的潜在研究方向。结论：通过公共数据库的生物信息检索，筛选出致病基因及其参与的机制通路，其中ITGA4、CD4、THY1、CD1D和IL2RB基因将可能成为新的分子生物标志物和靶向基因治疗目标。
Objective: To investigate the pathogenic genes and regulatory pathways of thymoma by compre-hensive bioinformatics analysis. Methods: GEO Gene Expression Omnibus database was retrieved and downloaded for 3 sets of thymoma gene microarray data, and the differential genes (DEGs) were screened by GEO2R, then GO, KEGG enrichment analysis and protein interaction network con-struction were performed for the differential genes by Metascape and STRING online software; then the pathogenic genes were screened by Cytoscape software; finally, the UALCAN and GEPIA data-bases were applied to validate the key genes, analyze their survival and explore the regulatory pathways. Results: Analysis of the three datasets yielded 1259 common DEGs, GO, KEGG enrichment analysis and SinoBiological website search showed that DEGs were involved in tumor necrosis factor signaling pathway, transmembrane receptor protein tyrosine kinase signaling pathway, TNF sig-naling pathway, PI3K-Akt signaling pathway, sphingolipid signaling pathway, Hippo signaling pathway, calcium signaling pathways, cancer pathways, transcriptional dysregulation in cancer and hematopoietic cell lines. 30 key pathogenic genes include ITGA4, ITGB3, ITGB5, ITGB6, ITGA8, ITGA11, COL6A1, THBS2, COL6A2, etc. Through validation, pathway exploration and survival analy-sis of the pathogenic genes: ITGA4, CD4, THY1, CD1D and IL2RB could all affect the overall survival of patients, suggesting a potential research direction for THY. Conclusion: The causative genes and their involved mechanistic pathways were screened by bioinformatics search of public databases, in which ITGA4, CD4, THY1, CD1D and IL2RB genes will likely become new molecular biomarkers and targets for targeted gene therapy.