基于miRNA-mRNA调控关系对与Cox回归模型的宫颈鳞状细胞癌预后生物标志物综合分析

Comprehensive Analysis of Prognostic Biomarkers in Cervical Squamous Carcinoma Based on Aberrant MiRNA-mRNA Axes and Cox Regression Models

目的:探究微小RNA(miRNA)-信使RNA(mRNA)关系对在宫颈鳞状细胞癌(CESC)中的表达,分析其预测CESC预后的意义。方法:利用癌症和肿瘤基因图谱(TCGA)数据库筛选CESC和正常宫颈组织中miRNA和mRNA的差异表达谱,利用miRTarBase、TargetScan和miRDB数据库验证miRNA与靶向mRNA的相互作用关系,并通过Cytoscape软件可视化,采用Kaplan-Meier生存分析确定CESC的预后标志物,构建与CESC预后相关的miRNAmRNA调控网络,并对筛选出的mRNA进行基因本体功能(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:通过比较CESC组织与正常宫颈组织,共检测到4个miRNA可纳入预后风险评分模型,生存分析筛选出9个与CESC预后相关的差异表达mRNA,最终得到与CESC预后紧密相关的4个miRNA-mRNA调控关系对,hsamiR-505-5p的靶向mRNA为染色质结构域蛋白8(CBX8),hsa-miR-142-3p分别靶向Ⅰ型血小板结合蛋白基序的解聚蛋白样金属蛋白酶3(ADAMTS3)、蛋白酪氨酸磷酸酶受体B(PTPRB)和SEC23同源物A(SEC23A)。生物学功能和通路分析显示,差异表达的mRNA主要在生物学过程和磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)、人乳头瘤病毒(HPV)感染的通路中显著富集。结论:miRNA-mRNA关系对与CESC预后相关,可作为今后CESC发病机制研究的新角度以及监测预后的有效指标。

Objective:To explore the expression of microRNA(miRNA)-messenger RNA(mRNA)and predict its prognostic significance in cervical squamous carcinoma(CESC),analyze its significance in predicting the prognosis of CESC.Methods:TCGA database was used to screen the differential expression profiles of miRNA and mRNA in CESC and normal cervical tissue.The interaction between miRNA and targeted mRNA was verified by miRTarBase,TargetScan and miRDB databases.The prognostic markers of CESC were determined by Kaplan-Meier survival analysis and visualized by Cytoscape software.Construction the miRNA-mRNA regulatory network related to the prognosis of CESC,the selected mRNAs were analyzed by gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Results:Four miRNAs and nine mRNAs differentially expressed in CESC and normal tissues were detected.Four miRNA-mRNA axes closely related to the prognosis of CESC were obtained.The target mRNA of hsa-miR-505-5p was CBX8,and hsa-miR-142-3p targeted ADAMTS3,PTPRB and SEC23A respectively.Biological function and pathway analysis showed that the differentially expressed mRNAs were mainly enriched in biological process and PI3K-Akt pathway,HPV infection pathway.Conclusions:Above miRNA-mRNA axes obtained in this study are related to the prognosis of CESC,which can be used as a new perspective for the study of the pathogenesis and an effective indicator for monitoring the prognosis of CESC.