Table_8_Prognostic Biomarkers on a Competitive Endogenous RNA Network Reveals Overall Survival in Triple-Negative Breast Cancer.xlsx

The objective of this study was to construct a competitive endogenous RNA (ceRNA) regulatory network using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with triple-negative breast cancer (TNBC) and to construct a prognostic model for predicting overall survival (OS) in patients with TNBC. Differentially expressed lncRNAs, miRNAs, and mRNAs in TNBC patients from the TCGA and Metabric databases were examined. A prognostic model based on prognostic scores (PSs) was established for predicting OS in TNBC patients, and the performance of the model was assessed by a recipient that operated on a distinctive curve. A total of 874 differentially expressed RNAs (DERs) were screened, among which 6 lncRNAs, 295 miRNAs and 573 mRNAs were utilized to construct targeted and coexpression ceRNA regulatory networks. Eight differentially expressed genes (DEGs) associated with survival prognosis, DBX2, MYH7, TARDBP, POU4F1, ABCB11, LHFPL5, TRHDE and TIMP4, were identified by multivariate Cox regression and then used to establish a prognostic model. Our study shows that the ceRNA network has a critical role in maintaining the aggressiveness of TNBC and provides comprehensive molecular-level insight for predicting individual mortality hazards for TNBC patients. Our data suggest that these prognostic mRNAs from the ceRNA network are promising therapeutic targets for clinical intervention.

本研究旨在利用三阴性乳腺癌（triple-negative breast cancer, TNBC）患者中差异表达的长链非编码RNA（long noncoding RNAs, lncRNAs）、微小RNA（microRNAs, miRNAs）及信使RNA（messenger RNAs, mRNAs），构建竞争性内源RNA（competitive endogenous RNA, ceRNA）调控网络，并建立用于预测三阴性乳腺癌患者总生存期（overall survival, OS）的预后模型。本研究对来自TCGA及Metabric数据库的三阴性乳腺癌患者的差异表达lncRNAs、miRNAs及mRNAs进行了分析。本研究基于预后评分（prognostic scores, PSs）构建了预测三阴性乳腺癌患者总生存期的预后模型，并通过受试者工作特征曲线（receiver operating characteristic, ROC）评估了该模型的性能。本研究共筛选出874个差异表达RNA（differentially expressed RNAs, DERs），其中6个lncRNAs、295个miRNAs及573个mRNAs被用于构建靶向及共表达竞争性内源RNA调控网络。本研究通过多因素Cox回归分析筛选出8个与生存预后相关的差异表达基因（differentially expressed genes, DEGs），即DBX2、MYH7、TARDBP、POU4F1、ABCB11、LHFPL5、TRHDE及TIMP4，并以此构建了预后模型。本研究表明，竞争性内源RNA调控网络在维持三阴性乳腺癌的侵袭性中发挥关键作用，可为预测三阴性乳腺癌患者的个体死亡风险提供全面的分子层面见解。本研究数据显示，来源于竞争性内源RNA调控网络的这些预后相关mRNAs有望成为临床干预的治疗靶点。