基于癌症基因组图谱数据库构建肝细胞癌相关miRNA-mRNA调控网络

Construction of hepatocellular carcinoma-related miRNA-mRNA regulatory network based on TCGA database

目的探讨肝细胞癌(HCC)发病机制,为HCC的诊断和临床治疗提供依据。方法基于癌症基因组图谱数据库,鉴定HCC样本与癌旁组织样本之间差异表达的miRNA与mRNA。通过miRDB、TargetScan数据库预测差异表达miRNA的靶基因,并与差异mRNA取交集确定目标基因。使用FunRich软件预测在HCC差异表达miRNA中的潜在转录因子。利用Bioconductor中的clusterProfiler包进行功能注释和途径富集分析。通过STRING数据库构建了蛋白质-蛋白质相互作用网络,对前20个枢纽基因进行表达验证和生存分析。结果对375例HCC样本、50例癌旁样本进行差异miRNA分析,共鉴定出300个差异表达的miRNA。对374例HCC样本、50例癌旁样本进行差异mRNA分析,共鉴定出1106个差异表达的mRNA。分别在上调的和下调的miRNA中选择20个差异表达最显著的miRNA预测其靶基因。对131个候选基因进行功能富集分析,结果显示主要与缬氨酸、亮氨酸和异亮氨酸降解,碳代谢以及催乳素信号通路等途径有关。结论在肝细胞癌中异常表达的miRNA-mRNA通路可能成为肝细胞癌诊断的新型生物标志物,为诊断和临床治疗提供依据。

Objective To investigate the pathogenesis of hepatocellular carcinoma(HCC)and provide the basis for its diagnosis and clinical treatment.Methods Differentially expressed miRNA and mRNA between HCC samples and adjacent tissue samples were identified based on the cancer genome atlas(TCGA)database.The target genes with differentially expressed miRNA were predicted by miRDB and TargetScan databases,and the intersection of miRNA with differentially expressed mRNA was determined.Prediction of potential transcription factors in differentially expressed miRNA in HCC using FunRich software.Functional annotation and pathway enrichment analysis were performed using the clusterProfiler package in Bioconductor.The protein-protein interaction network was constructed using a STRING database,and the miRNA-mRNA regulatory network was mapped by Cytoscape.Twenty miRNA with the most significant differential expression was verified and correlated survival analysis was performed.Results A total of 300 differentially expressed miRNA was identified in 375 HCC samples and 50 paracancerous samples by differential miRNA analysis.Totally 1106 diffe-rentially expressed mRNA was identified in differential mRNA analysis on 374 HCC samples and 50 paracancerous samples.Twenty miRNA with the most significant differential expression was selected from the up-regulated and down-regulated miRNA for target gene prediction.Functional enrichment analysis indicated that 131 candidate genes were mainly related to the regulation of valine,leucine and isoleucine degradation,carbon metabolism and prolactin signaling pathway.Conclusion The abnormally expressed miRNA-mRNA pathway in HCC may become a new biomarker for the diagnosis and provide the basis for diagnosis and clinical treatment.