基于ceRNA调控网络的乳腺癌预后相关生物标志物筛选

Screening of prognostic biomarkers for breast cancer based on ceRNA regulatory network

目的利用肿瘤基因组图谱(TCGA)数据库筛选差异表达mRNA、miRNA和lncRNA分子标签,构建预后相关的核心ceRNA调控子网络,探索其在乳腺癌预后相关生物标志物筛选中的作用。方法从TCGA下载乳腺癌患者的测序数据和临床数据,利用R包“Deseq2”和单因素COX比例风险回归模型,分别筛选差异表达且与预后相关的mRNA、miRNA和lncRNA分子标签,基于预测性数据库构建ceRNA网络,并对网络中的核心mRNA进行功能注释和免疫相关性分析。结果筛选出3个mRNA(KLF11、EDA、STXBP1)、1个lncRNA(XIST)和2个miRNA(hsa-miR-130a-3p、hsa-miR-195-5p)组成的核心ceRNA子网络,生存分析显示miRNA低表达、mRNA和lncRNA高表达,总生存期显著降低。结论核心ceRNA子网络中的6个RNA相互调节,可能通过免疫系统在乳腺癌发生发展中起重要作用,对预后产生影响。

Objective To screen the molecular labels of differentially expressed mRNA,miRNA and lncRNA by using The Cancer Genome Atlas(TCGA)database,and to construct a regulatory sub-network of core ceRNAs related to prognosis in order to explore its role in screening prognostic biomarkers of breast cancer.Methods The sequencing data and clinical data of breast cancer patients were downloaded from TCGA.Rpacket“Deseq2”and univariate COX proportional risk regression model were used to screen the molecular labels of differentially expressed mRNA,miRNA and lncRNA associated with prognosis.The ceRNA network was constructed based on the predictive database,and functional annotation and immune correlation analysis were conducted for core mRNAs in the network.Results Three mRNAs(KLF11,EDA,STXBP1),1lncRNA(XIST)and 2 miRNAs(hsa-miR-130a-3p,hsa-miR-195-5p)were screened out to construct the core ceRNA sub-network.Survival analysis showed that there were low miRNA expression,high mRNA and lncRNA expressions,and significantly reduced overall survival.Conclusion The 6RNAs in the core ceRNA sub-network regulate each other,which may play an important role in the occurrence and development of breast cancer through the immune system,as well as affect the prognosis.