hsa-miR-106b-5p调控ESR1表达对肝细胞癌患者生存预后的意义

Significance of hsa-miR-106b-5p on the survival and prognosis in patients with hepatocellular carcinoma by regulating the ESR1 expression

目的利用生物信息学方法,分析hsa-miR-106b-5p调控ESR1在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及其生存预后意义。方法利用BART和StarBase数据库筛选GSE108724芯片的差异miRNAs及其与HCC患者生存预后的关系;利用TargetScan和MetaScape数据库分析miRNAs的靶基因及其GO和KEGG富集分析,并利用String数据库和Cytoscape软件筛选靶基因中的HUB基因;对HUB基因进行生存预后分析及其与miRNAs的结合位点分析;通过临床数据构建HUB基因在HCC中的风险预测模型,并利用C-index、校准曲线(CC)、决策曲线分析(DCA)以及ROC曲线对预测模型进行评价。结果共得到5个差异miRNAs,仅hsa-miR-106b-5p对HCC患者生存预后有显著意义;hsa-miR-106b-5p的靶基因有644个,其KEGG主要富集在Rap1信号通路、MAPK信号通路和癌症信号通路上;GO功能主要富集在跨膜受体蛋白酪氨酸激酶、Ras GTPase结合和分解代谢调控等上;HUB基因中仅ESR1在HCC中低表达,并对HCC患者的生存预后有显著意义,且ESR1 mRNA 3’UTR直接与hsa-miR-106b-5p结合;Logistic回归分析发现低表达的ESR1是HCC患者生存预后的独立危险因素;且所构建的风险预测模型具有较好的准确性和有效性。结论hsa-miR-106b-5p调控ESR1使其在HCC中低表达,且不利于HCC患者的生存预后,可作为HCC的潜在治疗靶点。

Objective To analyze the significance of hsa-miR-106b-5p on the survival and prognosis in patients with hepatocellular carcinoma(HCC)through regulating the ESR1 expression by using the bioinformatics methods.Methods The BART and StarBase databases were used to screen the differential miRNAs of the GSE108724 and their relationship with the survival prognosis of HCC patients.The TargetScan and MetaScape databases were used to analyze the target genes of miRNAs and their GO and KEGG enrichment analysis,and the String database and Cytoscape software were used to screen the HUB gene of the target gene.The survival and prognosis of the HUB gene and its binding site with miRNAs were analyzed.A risk prediction model of the HUB genes was constructed in HCC patients through clinical data,and the C-index,Calibration Curve,Decision Curve Analysis and ROC Curve were used to evaluate the prediction model.Results A total of 5 differential miRNAs were obtained.Only hsa-miR-106b-5p had significance for the survival and prognosis of HCC patients.Hsa-miR-106b-5p had 644 target genes,and its KEGG was mainly enriched in Rap1 signaling pathway,MAPK signaling pathway and cancer signaling pathway.GO functions were mainly enriched in transmembrane receptor protein tyrosine kinase,Ras GTPase binding and catabolism regulation.Among the HUB genes,only ESR1 was low-expressed in HCC and had significance for the survival prognosis of HCC patients,and ESR1 mRNA 3’UTR directly binds to hsa-miR-106b-5p.Logistic regression analysis found that low expression of ESR1 was the independent risk factors in the survival prognosis of HCC patients,and the constructed risk prediction model had good accuracy and effectiveness.Conclusion Hsa-miR-106b-5p regulates the low expression of ESR1 in HCC,and is not conducive to the prognosis of HCC patients,and can be used as a potential therapeutic target for HCC.