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竞争性内源性RNA网络上的预后生物标志物揭示三阴性乳腺癌的总生存期

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

作者信息

Qin Wenxing, Qi Feng, Li Jia, Li Ping, Zang Yuan-Sheng

机构信息

Department of Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Front Oncol. 2021 Jun 11;11:681946. doi: 10.3389/fonc.2021.681946. eCollection 2021.

Abstract

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.

摘要

本研究的目的是利用三阴性乳腺癌(TNBC)患者中差异表达的长链非编码RNA(lncRNA)、微小RNA(miRNA)和信使RNA(mRNA)构建竞争性内源性RNA(ceRNA)调控网络,并构建预测TNBC患者总生存期(OS)的预后模型。检测了来自TCGA和Metabric数据库的TNBC患者中差异表达的lncRNA、miRNA和mRNA。建立了基于预后评分(PS)的预后模型来预测TNBC患者的OS,并通过受试者工作特征曲线评估该模型的性能。共筛选出874个差异表达RNA(DER),其中6个lncRNA、295个miRNA和573个mRNA用于构建靶向和共表达ceRNA调控网络。通过多变量Cox回归鉴定出8个与生存预后相关的差异表达基因(DEG),即DBX2、MYH7、TARDBP、POU4F1、ABCB11、LHFPL5、TRHDE和TIMP4,然后用于建立预后模型。我们的研究表明,ceRNA网络在维持TNBC的侵袭性方面起关键作用,并为预测TNBC患者的个体死亡风险提供了全面的分子水平见解。我们的数据表明,来自ceRNA网络的这些预后mRNA是临床干预中很有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a69f/8232227/537d98fd8678/fonc-11-681946-g001.jpg

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