整合高通量数据探讨非小细胞肺癌组织中微小RNA-182-5p的潜在靶基因

Integrating High-Throughput Data to Explore Target Genes of MicroRNA-182-5p in Non-small Cell Lung Cancer

目的探讨miR-182-5p在非小细胞肺癌(NSCLC)中的表达情况、潜在靶基因、临床意义以及作用机制。方法通过联合高通量数据以及内部逆转录定量聚合酶链反应(RT-qPCR)数据的1720个样本,整合分析miR-182-5p在NSCLC中的表达情况。绘制受试者工作特征(ROC)曲线和综合受试者工作特征(SROC)曲线以评估miR-182-5p鉴别NSCLC组织和正常肺组织的能力。应用miRWalk 3.0数据库在线预测miR-182-5p的潜在靶基因,对低表达的潜在靶基因进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路分析。使用STRING在线工具构建miR-182-5p潜在靶基因的蛋白互作网络。运用Spearman相关系数评估潜在靶基因与miR-182-5p表达的相关性。结果与正常肺组织对比,miR-182-5p在NSCLC组织中呈高表达,标准化均数差(SMD)为1.33(0.93~1.74)。miR-182-5p区分NSCLC和正常肺组织的曲线下面积(AUC)为0.95(0.92~0.96),敏感度为0.81(0.68~0.89),特异度为0.93(0.86~0.96)。miR-182-5p与EPS15的表达水平存在负相关性(ρ=-0.235,P=0.001)。结论与正常肺组织相比,NSCLC组织中miR-182-5p高表达。EPS15有可能是miR-182-5p在NSCLC的新靶点。

Objective To explore the expression,target genes,clinical significance and mechanism of miR-182-5p in non-small cell lung cancer(NSCLC).Methods Combining 1720 samples from high throughput data and in-house real time quantitative polymerase chain reaction(RT-qPCR),the expression of miR-182-5p in NSCLC by calculating standardized mean difference(SMD)was comprehensively analyzed.Meanwhile,receiver operator characteristic(ROC)curves and summary ROC(SROC)curve were used to evaluate the ability of miR-182-5p to identify NSCLC tissues and normal lung tissues.The potential target genes of miR-182-5p were predicted using miRWalk 3.0 database.Based on these genes,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analyses were performed.Protein-protein interaction network of the potential target genes of miR-182-5p was constructed by using the online tool STRING.Spearman correlation coefficient was used to evaluate the correlation between potential target genes and miR-182-5p expression.Results Compared with normal lung tissues,miR-182-5p was highly expressed in NSCLC tissues with a standardized mean difference(SMD)of 1.33(0.93-1.74).The area under the curve(AUC),the sensitivity,and the specificity of miR-182-5p identifying NSCLC were 0.95(0.92-0.96),0.81(0.68-0.89),and 0.93(0.86-0.96),respectively.There was a negative correlation between miR-182-5p and the expression level of EPS15(ρ=-0.235,P=0.001).Conclusion Compared to normal lung tissue,upregulated miR-182-5p expression was detected in NSCLC tissue.EPS15 may be a novel target of miR-182-5p in NSCLC.