经肝动脉化疗栓塞治疗肝细胞癌患者疗效的生物信息学分析

Bioinformatics analysis of the efficacy of transhepatic arterial chemoembolization in patients with hepatocellular carcinoma

目的通过生物信息学寻找经肝动脉化疗栓塞(TACE)治疗肝细胞癌患者疗效的差异基因(DEGs)并深入分析其功能。方法从基因表达数据库(GEO)中下载微阵列数据集GSE104580;利用在线工具GEO2R筛选DEGs;运用R语言"ClusterProfiler"数据包对筛选得到的TACE疗效的DEGs进行GO功能和KEGG通路富集分析;使用STRING数据库构建关键差异基因的蛋白质互作网络,应用Cytoscape软件筛选出TACE疗效差异的关键DEGs。利用UALCAN和GEPIA数据库分别对TACE疗效差异关键DEGs的表达和生存进行分析,使用Log-rank检验方法。结果439个基因在TACE治疗肝细胞癌中表达有明显差异,其中上调基因228个,下调基因217个;差异基因的富集及其通路主要包括白细胞介素17(IL-17)信号通路、肿瘤转录失调和视黄醇代谢等生物过程;Cytoscape共筛选出10个TACE疗效差异的关键DEGs。最后通过多数据库综合分析发现,筛选出的10个TACE疗效差异的关键DEGs均与肝细胞癌患者预后密切相关。高表达组CDK1、TOP2A、CDC20、BUB1、KIF2C、DLGAP5、CENPF、TPX2、BIRC5和TTK肝癌患者总体生存率均显著低于低表达组患者,其结果具有统计学意义(P<0.05)。结论筛选出的10个基因对TACE治疗肝细胞癌患者的耐药分子机制以及进行个体化精准治疗提供依据。

Objective To find the differentially expressed genes(DEGs)for the efficacy of transhepatic artery chemoembolization(TACE)in patients with hepatocellular carcinoma(HCC)by bioinformatics and to analyze their functions,so as to provide a theoretical basis for studying chemoresistance in HCC.Methods The microarray dataset GSE104580 was downloaded from the Gene Expression Database(GEO);the DEGs were screened using the online tool GEO2R;the R language"ClusterProfiler"data package was used to perform GO function and KEGG enrichment analysis on the screened DEGs for TACE efficacy;the STRP was used to enrich the enrichment analysis of DEGs.The expression and survival of the key DEGs were analyzed by UALCAN and GEPIA databases respectively.The Log-rank test was used for statistical analysis.Results Totally,439 genes were significantly differentially expressed in TACE for HCC.Among them,228 genes were up-regulated and 217 genes were down-regulated.The enrichment of differential genes and their pathways mainly included biological processes such as interleukin 17(IL-17)signaling pathway,tumor transcriptional dysregulation and retinol metabolism.Cytoscape screened a total of 10 key DEGs for differential TACE efficacy.Finally,a comprehensive multi-database analysis revealed that the 10 key DEGs screened for differences in TACE efficacy were all closely related to the prognosis of HCC patients.The overall survival rates of HCC patients with CDK1,TOP2A,CDC20,BUB1,KIF2C,DLGAP5,CENPF,TPX2,BIRC5 and TTK in the high expression group were significantly lower than those of patients in the low expression group,and the results were statistically significant(P<0.05).Conclusion The 10 genes screened provide theoretical basis for the molecular mechanism of drug resistance in patients with HCC treated with TACE and for individualized and precise treatment.