基于生物信息学筛选和验证头颈部鳞状细胞癌的诊断标志物microRNA-381-3p

Screening and validation of microRNA-381-3p as a diagnostic biomarker for head and neck squamous cell carcinoma based on bioinformatics

目的筛选并验证头颈部鳞状细胞癌(HNSCC)的microRNA(miRNA)诊断标志物,为HNSCC的早期临床诊断提供新的生物标志物。方法提取基因表达综合数据库和癌症基因组图谱(TCGA)数据库的miRNA表达数据,分为训练集和验证集。在训练集中利用Limma R软件包筛选HNSCC组织和正常组织中差异表达的miRNA,并确定miR-381-3p为研究目标。使用实时荧光定量聚合酶链反应验证miR-381-3p的表达水平。利用受试者操作特征(ROC)曲线的曲线下面积(AUC)评估miR-381-3p的诊断效能。使用在线网站筛选miR-381-3p的靶基因并利用ClusterProfile包对靶基因进行京都基因与基因组数据库(KEGG)富集分析。使用蛋白质—蛋白质相互作用网络和Cytoscape软件进一步筛选靶基因中的核心基因。结果miR-381-3p的表达水平在HNSCC组织中下调。ROC分析表明miR-381-3p在不同的数据集中具有稳定的诊断能力(AUC>0.700)。临床分析显示miR-381-3p表达水平与HNSCC患者的T分期和临床分期显著相关。进一步的KEGG分析显示miR-381-3p的靶基因富集到丝裂原激活蛋白激酶相关信号通路和其他HNSCC相关信号通路。结论miR-381-3p可以区分HNSCC患者和健康人群,是HNSCC的潜在诊断标志物。

Objective To screen and verify the microRNA(miRNA)biomarkers for head and neck squamous cell carcinoma(HNSCC),and provide a novel biomarker for the early diagnosis of HNSCC.Methods The miRNA microarray data from gene expression omnibus(GEO)and the cancer genome atlas(TCGA)database were downloaded and divided into training cohort and validation cohort.Limma R package was used to identify differentially expressed miRNAs(DEmiRNAs)between HNSCC tissues and normal tissues,and miR-381-3p was selected as the target gene.The expression level of miR-381-3p in HNSCC and normal tissues were identified by real-time fluorescence quantitative polymerase chain reaction.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate the diagnostic capability of miR-381-3p.The target genes of miR-381-3p were predicted using online datasets.The Kyoto Encyclopedia of Genes and Genome(KEGG)were performed by ClusterProfile package.The protein-protein interaction network and Cytoscape software were used to further identify the hub genes.Results The expression levels of miR-381-3p were down-regulated in HNSCC tissues.ROC analysis showed that miR-381-3p had stable diagnostic capability in different datasets(AUC>0.700).Clinical correlation analysis showed that the expression level of miR-381-3p was significantly correlated with the T stage and clinical stage of HNSCC patients.Further KEGG analysis showed that the target genes of miR-381-3p might participate in the MAPK signaling pathway and other HNSCC related signaling pathways.Conclusion miR-381-3p can distinguish HNSCC patients from healthy people,and may serve as a potential diagnostic biomarker of HNSCC.