食管癌坏死性凋亡关键基因的筛选与验证

Screening and verification of key genes of necroptosis in esophageal carcinoma

目的:运用生物信息学分析以及验证坏死性凋亡基因在食管癌中的潜在作用机制。方法:利用生物信息学技术对数据集GSE38129行差异表达分析并与坏死性凋亡基因组交叉获取坏死性凋亡的差异基因(NRDEGs)。采用基因集富集分析评价食管癌的基因富集信号通路。利用STRING数据库和Cytoscape软件可视化蛋白质-蛋白质相互作用(PPI)网络,鉴定NRDEGs中的Hub基因。利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)对NRDEGs进行了富集分析。利用Network Analyst数据库预测坏死性凋亡相关转录因子-靶基因调控网络,CIBERSORT算法分析免疫浸润模式,探讨免疫细胞类型与Hub基因表达的相关性。为了确定组间相关性,进行了Spearman秩检验。结果:共筛选出29个NRDEGs。NRDEGs主要参与坏死性凋亡、甲型流感、NOD-样受体信号通路。预测了113个NRDEGs相关转录因子,并且发现食管癌中CD4+T细胞和树突状细胞活化明显失衡(Hub基因与CD4+T细胞和树突状细胞呈正相关)。结论:NRDEGs(29个基因)与食管癌的发生发展相关,其可能通过介导肿瘤的免疫机制参与食管癌的病理生理过程。

Objective Bioinformatics analysis was used to explore and verify the potential mechanism of necroptosis gene in esophageal carcinoma.Methods The differential expression of data set GSE38129 was analyzed by bioinformatics technology and the necroptosis differential genes(NRDEGs)were obtained by crossing with necroptosis genome.Gene set enrichment analysis was used to evaluate gene enrichment signaling pathways in esophageal carcinoma(ESCC).The STRING database and Cytoscape software were used to visualize protein-protein interaction(PPI)networks and identify Hub genes of NRDEGs.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of NRDEGs was also performed.The Network Analyst database was used to predict the necrotizing apoptosis-related transcription factor-target gene regulatory network,the CIBERSORT algorithm was used to analyze the pattern of immune infiltration,and the correlation between the abundance of immune cell types and Hub gene expression was investigated.Spearman rank test was performed to determine the correlation between groups.Results A total of 29 NRDEGs were identified.NRDEGs were mainly involved in Necroptosis,Influenza A,NOD-like receptor signaling pathway.Subsequently,we predicted 113 NRDEGS-related transcription factors.The imbalance of T cells CD4 memory resting and Dendritic cell activated was obviously observed was found in ESCC(Hub gene was positively correlated with CD4+T cells and dendritic cells).Conclusion NRDEGs(29 genes)were associated with the occurrence and development of ESCC,and may be involved in the pathophysiology of ESCC by mediating the immune mechanism.