肾透明细胞癌中lncRNA和miRNA差异表达及相关ceRNA调控网络的分析研究

Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma

本文旨在通过大样本基因组学分析技术,评估lncRNA、miRNA、mRNA及ceRNA在肾透明细胞癌中的差异表达情况及其预后价值。利用R软件对TCGA数据库中肾透明细胞癌RNA和miRNA数据进行基因差异表达分析和生存分析,并通过cytoscape软件得到差异表达的lncRNA-miRNA-mRNA之间的ceRNA调控关系网。结果发现共有1 570个lncRNA、54个miRNA和17个mRNA在肾透明细胞癌组织中存在异常表达,且其表达水平以上调为主(错误发现率<0.01;对数差异表达倍数变化绝对值> 2)。ceRNA调控网显示共89个差异表达的lncRNA和9个差异表达的miRNA之间存在相互作用关系,生存分析共鉴定出COL18A1-AS1、TCL6、LINC00475、UCA1、WT1-AS、HOTTIP、PVT1等38个有预后价值的lncRNA和2个有预后价值的miRNA(miR-21和miR-155)(P <0.05)。本研究将为肾透明细胞癌靶向治疗与预后评估提供新的理论依据。

To evaluate the differential expression profiles of the lncRNAs,miRNAs,mRNAs and ceRNAs,and their implication in the prognosis in clear cell renal cell carcinoma(CCRCC),the large sample genomics analysis technologies were used in this study.The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas(TCGA)database,and R software was used for gene expression analysis and survival analysis.Cytoscape software was used to construct the ceRNA network.The results showed that a total of 1 570 lncRNAs,54 miRNAs,and 17 mRNAs were differentially expressed in CCRCC,and most of their expression levels were up-regulated(false discovery rate<0.01 and absolute log fold change>2).The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs.Further survival analysis revealed that 38 lncRNAs(including COL18A1-AS1,TCL6,LINC00475,UCA1,WT1-AS,HOTTIP,PVT1,etc.)and 2 miRNAs(including miR-21 and miR-155)were correlated with the overall survival time of CCRCC(P<0.05).Together,this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.