基于生物信息学鉴定黏液样脂肪肉瘤中甲基化调控的差异表达基因

Identification of methylation-regulated differentially expressed genes in myxoid liposarcoma:a bioinformatics-based study

目的通过生物信息学方法鉴定黏液样脂肪肉瘤(MLPS)中甲基化调控的差异表达基因(MeDEGs)。方法从GEO数据库中选取MLPS基因数据集GSE59568和DNA甲基化数据集GSE52391。采用GEO2R工具筛选差异表达基因(DEGs)和差异甲基化基因(DMGs),重叠负相关的DEGs和DMGs以筛选MeDEGs。采用DAVID软件对MeDEGs进行功能分析及通路富集分析。利用STRING和Cytoscape等工具绘制蛋白互作网络、筛选功能模块与Hub基因。利用TCGA数据库分析Hub基因在肉瘤中的甲基化水平和基因表达水平,及其与肉瘤患者生存情况的关系。结果共鉴定出221个MeDEGs,包括143个表达上调基因和78个表达下调基因。MeDEGs主要参与细胞增殖、凋亡、核糖体结构成分、蛋白结合等生物学过程,主要富集在核糖体、癌症、RAS相关蛋白1、AMP依赖的蛋白激酶和Ras等信号通路。筛选出的前20个Hub基因均为上调的MeDEGs,其中RPS2、CDCA5、NCAPG、NLE1、TYMS和BYSL可能是MLPS患者预后潜在的独立预测因子。结论RPS2、CDCA5、NCAPG、NLE1、TYMS和BYSL等基因的异常甲基化可能与MLPS的发生及预后密切相关。

Objective To identify methylation-regulated differentially expressed genes(MeDEGs)by bioinformatic method in myxoid liposarcoma(MLPS).Methods The genetic dataset GSE59568 and DNA methylation dataset GSE52391 of MLPS were selected from the GEO database.GEO2R tool was used to screen differentially expressed genes(DEGs)and differentially methylated genes(DMGs),MeDEGs were screened by overlapping DEGs and DMGs exhibiting a negative correlation.DAVID software was applied to function analysis and pathway enrichment analysis of MeDEGs.Protein-protein interaction network was visualized,and function module and Hub genes were filtered using STRING,Cytoscape and other tools.TGGA database was employed to analyze the methylation and mRNA expression levels of Hub genes in sarcoma,as well as their relationship with survival in sarcoma patients.Results A total of 221 MeDEGs were identified,including 143 up-regulated and 78 down-regulated expression genes.MeDEGs mainly involved in cell proliferation,apoptosis,ribosome structural components,protein binding and other biological processes,commonly enriched in ribosome,cancer,RAS-associated protein 1,AMP-activated protein kinase,Ras and other signaling pathways.The former 20 Hub genes screened out were up-regulated MeDEGs,in which RPS2,CDCA5,NCAPG,NLE1,TYMS,and BYSL might be the potential independent predictors of prognosis in patients with MLPS.Conclusion The abnormal methylation of genes such as RPS2,CDCA5,NCAPG,NLE1,TYMS and BYSL may be closely related to the occurrence and prognosis of MLPS.