基于生物信息学和转录组测序分析血管肉瘤细胞和血管肉瘤干细胞样细胞来源外泌体差异表达谱

Bioinformatics and transcriptome sequencing analysis of differential expression profile of angiosarcoma cells and angiosarcoma stem-like cells derived exosomes

目的:借助生物信息学分析探究血管肉瘤细胞ISOHAS与血管肉瘤干细胞样细胞Sphere来源外泌体的关键差异表达基因(DEGs)及富集的生物学功能与信号通路,探寻血管肉瘤新的治疗靶点。方法:对ISOHAS与Sphere来源外泌体进行转录组测序,以|log2FC|>2、FDR<0.05为标准筛选两种细胞来源外泌体DEGs,通过生物信息学分析对DEGs进行GO和KEGG通路富集分析,识别富集DEGs的生物学功能和信号通路,利用STRING数据库筛选关键DEGs。利用iPath对代谢途径进行可视化分析,确定DEGs富集的代谢途径。结果:转录组测序结果显示,ISOHAS与Sphere来源外泌体有91个DEGs;GO和KEGG通路富集分析显示,DEGs主要富集的生物学功能和信号通路分别为对糖皮质激素的反应、TNF信号通路,STRING数据库显示TNF、IL-6为关键DEGs。iPath代谢网络分析显示DEGs主要集中于脂质代谢、核苷酸代谢。结论:Sphere来源外泌体可能通过携带关键基因TNF、IL-6干预糖皮质激素反应、TNF信号通路、脂质代谢、核苷酸代谢等生物学功能和信号通路,对血管肉瘤发生发展产生影响,为血管肉瘤治疗提供了新靶点。

Objective:To investigate key differential expressed genes(DEGs),enriched biological functions and signaling pathways in exosomes derived from angiosarcoma cells ISOHAS and angiosarcoma stem-like cells Sphere by bioinformatics analysis,to provide new therapeutic targets for angiosarcoma.Methods:Transcriptome sequencing of exosomes derived from ISOHAS and Sphere were performed to screen for DEGs by|log2FC|>2 and FDR<0.05 as criteria.Bioinformatics analysis was used to enrich GO and KEGG pathways of DEGs to identify biological functions and signaling pathways of enriched DEGs.STRING database was used to screen key DEGs,and iPath was used to visualize to identify metabolic pathways enriched by DEGs.Results:Transcriptome sequencing results showed that 91 DEGs were identified in exosomes derived from ISOHAS and Sphere.GO and KEGG pathway enrichment analysis demonstrated that main biological functions and signaling pathways enriched by DEGs were response to glucocorticoid and TNF signaling pathway,respectively.STRING database demonstrated that TNF and IL-6 were key DEGs.iPath metabolic network analysis demonstrated that DEGs were mainly identified in lipid metabolism and nucleotide metabolism.Conclusion:Sphere-derived exosomes may influence occurrence and development of angiosarcoma by carrying key genes TNF and IL-6 to interfere with glucocorticoid response,TNF signal ing pathway,lipid metabolism,nucleotide metabolism and other biological functions and signaling pathways,providing new ideas for therapeutic targets for angiosarcoma.