基于生物信息学的hsa-miR-155-5p通过PTEN调控中央记忆T细胞/辅助T细胞对肝细胞癌免疫微环境的影响研究

Effect of hsa-miR-155-5p on the Immune Microenvironment of Hepatocellular Carcinoma by Regulating Central Memory T Cells Helper T Cells Through PTEN Based on the Bioinformatics Method

目的运用生物信息学方法预测人类miR-155-5p靶基因,进一步探索其在肝细胞癌(HCC)中的功能。方法通过starBase数据库筛选出hsa-miR-155-5p靶基因,DAVID和Reactome数据库进行功能富集分析。蛋白-蛋白相互作用网络分析靶基因之间的相互关系,cytohubba插件获得关键基因。Kaplan-Meier生存分析进一步筛选关键基因,ssGSEA算法分析HCC免疫浸润情况,Spearman相关系数分析关键基因与免疫浸润的相关性。结果共筛选出1493个hsa-miR-155-5p靶基因;靶基因GO富集分析集中于调控转录、蛋白质分解代谢过程、细胞周期的调节;KEGG生物通路主要富集于AMPK信号通路、PI3K-Akt信号通路和FoxO信号通路、以及子宫内膜癌、胰腺癌和肝细胞癌等疾病通路。利用蛋白互作网络共获得30个关键基因,与HCC信号通路基因取交集获得GSK3B、PTEN、PIK3R1、EGFR、CCND1、SMAD2、PIK3CA、RPS6KB1、KRAS、SOS1等10个关键基因。生存分析显示,PTEN高表达的HCC患者的预后优于低表达患者。PTEN表达量与中央记忆T细胞、辅助T细胞的免疫浸润均呈现较强的正相关性。结论hsa-miR-155-5p通过下游靶基因PTEN调控中央记忆T细胞、辅助T细胞,进而影响HCC免疫浸润微环境,或可为HCC发生机制和临床治疗的探索提供帮助。

Objective To predict the target genes of human miR-155-5p by bioinformatics methods,and to further explore its function in hepatocellular carcinoma(HCC).Methods The target genes of hsa-miR-155-5p were screened by starBase database,and functional enrichment analysis was performed by DAVID and Reactome databases.Protein-protein interaction network was used to analyze the relationship between target genes,and cytohubba plug-in was used to obtain key genes.Kaplan-Meier survival analysis was used to further screen key genes,ssGSEA algorithm was used to analyze the immune infiltration of HCC,and Spearman correlation coefficient was used to analyze the correlation between key genes and immune infiltration.Results A total of 1493 hsa-miR-155-5p target genes were screened.GO enrichment analysis of target genes focused on the regulation of transcription,protein catabolic process and cell cycle regulation.The KEGG biological pathway was mainly enriched in AMPK signaling pathway,PI3K-Akt signaling pathway and FoxO signaling pathway,as well as endometrial cancer,pancreatic cancer and hepatocellular carcinoma.A total of 30 key genes were obtained by protein interaction network,and 10 key genes such as GSK3B,PTEN,PIK3R1,EGFR,CCND1,SMAD2,PIK3CA,RPS6KB1,KRAS and SOS1 were obtained by intersection with Hepatocellular carcinoma signaling pathway genes.Survival analysis showed that the prognosis of HCC patients with high expression of PTEN was better than that of patients with low expression.The expression of PTEN was positively correlated with the immune infiltration of central memory T cells and helper T cells.Conclusion hsa-miR-155-5p regulates central memory T cells and helper T cells through the downstream target gene PTEN,thereby affecting the immune infiltration microenvironment of HCC,which may provide help for the exploration of HCC pathogenesis and clinical treatment.