miR-182作为胃癌潜在生物学标志物的Meta分析及生物信息学分析

miR-182 as Potential Biomarker for Gastric Cancer:A Meta-analysis and Bioinformatics Analysis

目的研究miR-182在胃癌中的表达,分析其作为胃癌生物学标志物的诊断价值及相关的分子机制。方法从GEO、TCGA及数据库获取miR-182的表达数据,使用Stata14.0软件分别对胃癌患者组织和血液/血清中miR-182的表达进行Meta分析和诊断性Meta分析。运用5个预测数据库预测miR-182的靶基因,通过GO、KEGG富集分析及蛋白质相互作用(PPI)网络分析探索miR-182在胃癌中的生物学功能和关键基因(Hub基因)。结果共纳入20个研究,包括13个胃癌组织研究和7个血液/血清研究。通过随机效应模型(SMD=1.09,95%CI:0.26~1.92)发现miR-182在胃癌组织中显著增加(I 2=96.3%,P=0.000)。此外,SROC曲线下面积、特异性和敏感度分别为0.76、0.75和0.65。在胃癌患者的血液/血清中,miR-182同样显著上调(SMD=3.37,95%CI:2.15~4.59,I 2=97.8%,P=0.000)。SROC曲线下面积、特异性和敏感度分别为0.90、0.72和0.90。GO和KEGG富集分析表明,miR-182的靶基因与多种重要通路有关。最后,通过PPI分析筛选出4个Hub基因(NRAS、CREB1、FBXW7和SOX2)。结论miR-182在胃癌样本中上调,可能通过靶向其靶基因在胃癌中发挥重要作用,其可能是胃癌诊断的潜在生物学标志物。

Objective To investigate the expression of miR-182 in gastric cancer(GC),and to analyze its diagnostic value and related molecular mechanism as a biomarker for GC.Methods We extracted the data of miR-182 expression from the Gene Expression Omnibus(GEO),the Cancer Genome Atlas(TCGA)and databases.For miR-182 expression of tissues and blood/serum in GC patients,we used Stata14.0 to conduct Meta-analysis and diagnostic Meta-analysis.We predicted the target genes of miR-182 through using 5 prediction databases.Subsequently,the biological function and hub genes of miR-182 in GC were explored by gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and protein-protein interaction(PPI)networks analyses.Results A total of 20 studies were recruited,including 13 studies in the tissue group and 7 studies in the blood/serum group.In GC tissues,the miR-182 was significantly increased based on random-effects model(standard mean difference,SMD=1.09,95%CI:0.26-1.92,I 2=96.3%,P=0.000).In addition,the summarized receiver operating characteristic(SROC)curve,specificity and sensitivity were 0.76,0.75 and 0.65,respectively.Consistently,in blood/serum of GC patients,the miR-182 was significantly up-regulated(SMD=3.37,95%CI:2.15-4.59,I 2=97.8%,P=0.000).The SROC illustrated that AUC was 0.90.The specificity and sensitivity in the blood group of GC were 0.72 and 0.90.KEGG and GO analyses revealed that the target genes are related to various key pathways.Finally,four genes(NRAS,CREB1,FBXW7 and SOX2)were defined as hub genes of miR-182 via PPI analyses.Conclusion MiR-182 is up-regulated in GC samples and may play an important role in GC by targeting its target genes,which may be potential biomarker for the diagnosis of GC.