亚洲人群肝细胞癌mRNA-miRNA表达谱整合分析挖掘疾病治疗靶点

目的通过整合数据库分析筛选出与亚洲人肝细胞癌(HCC)生存期相关微小RNA(miRNA),并探讨该miRNA潜在的生物学调控网络。方法利用癌症基因组图谱(TCGA)数据库获取亚洲人群HCC癌组织编码基因(mRNA)和miRNA表达量数据集,采用perl语言和R语言对数据进行提取、整理和分析,利用加权基因共表达网络(WGCNA)获取miRNA的共表达基因,并对筛选得到的差异表达miRNA进行Kaplan-Meier生存分析,筛选出对总生存时间存在影响的miRNA。通过与WGCNA筛选得到的共表达基因和miRNA靶基因预测数据库miRPathDB结合探寻其潜在靶基因,并通过metascape网站进行功能预测。结果通过TCGA共下载到6例正常、126例HCC癌组织的mRNA表达量数据集和6例正常、166例HCC癌组织的miRNA表达量数据集,通过生物信息学分析筛选出hsa-mir-139-5p差异表达具有显著意义,且对HCC总生存期有显著影响,通过预测其靶基因,发现其与脂质代谢、碳代谢等代谢通路相关。结论hsamir-139-5p可作为潜在的HCC治疗靶点,但需要后续实验验证。利用生物信息学手段筛选生物标志物或治疗靶标,是一种高效而经济的研究方式。

Integrative analysis of mRNA-miRNA expression profiles of hepatocellular carcinoma in Asian populations to identify potential therapeutic targets

AIM To explore hepatocellular carcinoma(HCC)related microRNAs(miRNA)by analyzing HCC dataset in Asian populations,and to explore its potential biological regulatory network.METHODS HCC mRNA and miRNA expression datasets were obtained from TCGA.The data were extracted,collated and analyzed by perl and R language.Weighted gene co-expression network(WGCNA)was used to obtain the co-expression genes of miRNAs,and Kaplan-Meier survival analysis was used to evaluate the effect of these differentially expressed miRNAs.The potential target genes were explored by combining the co-expression genes screened by WGCNA with miRPathDB database,and functional enrichment analysis for these potential target genes was carried out through metascape.RESULTS A total of 6 normal and 126 HCC samples of mRNA expression dataset,and 6 normal and 166 HCC samples of miRNA expression dataset were downloaded from TCGA.One miRNA,hsa-mir-139-5 p,was seen differentially expressed in normal and HCC samples,and had significant impact on the overall survival of HCC patients.After enrichment analysis of its potential target genes,hsa-mir-139-5 p were found to be related to lipids metabolism,carbon metabolism and other metabolic pathways.CONCLUSION Hsa-mir-139-5 p may be a potential target for HCC treatment,but it needs to be verified by further experimental.Screening biomarkers or therapeutic targets by data mining is a cost-effective way.