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鉴定与乳腺癌预后相关的新型 lncRNA-miRNA-mRNA ceRNA 网络。

Identification of a novel lncRNA-miRNA-mRNA competing endogenous RNA network associated with prognosis of breast cancer.

机构信息

Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, P. R. China.

出版信息

J Biochem Mol Toxicol. 2022 Aug;36(8):e23089. doi: 10.1002/jbt.23089. Epub 2022 May 9.

Abstract

Recently, the effects of competing endogenous RNA (ceRNA) on molecular biological mechanism of cancer have aroused great interest. In this study, long noncoding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) ceRNA network was screened and constructed based on the Cancer Genome Atlas (TCGA) database, and its efficacy in predicting the prognosis of breast cancer patients was evaluated. The RNA-sequencing, miRNA-sequencing, and corresponding clinical information were downloaded from the TCGA database, and differentially expressed genes were screened after data searching. The similarity between two groups of genes was analyzed by weighted correlation network analysis (WGCNA). Next, the interaction among lncRNA, miRNA, and mRNA was predicted followed construction of the lncRNA-miRNA-mRNA ceRNA network. Finally, univariate and multivariate Cox regression analysis was used to screen prognostic factors to construct prognostic risk model. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of this model in predicting the prognosis of breast cancer patients. In total 5056 differentially expressed lncRNAs, 712 differentially expressed miRNAs, and 9878 differentially expressed mRNAs were identified in breast cancer tissues. WGCNA predicted that 823 lncRNAs and 1813 mRNAs were closely related to breast cancer. The lncRNA-miRNA-mRNA ceRNA network involved in breast cancer was constructed based on 27 lncRNA, 14 miRNAs, and 4 mRNAs. ZC3H12B, HRH1, TMEM132C, and PAG were the possible independent risk factors for the prognosis of breast cancer patients with the area under the signal characteristic curve under ROC curve of 0.609. This study suggested that the prognosis risk model based on ZC3H12B, HRH1, TMEM132C, and PAG1 accurately predicted the prognosis of breast cancer patients.

摘要

最近,竞争内源性 RNA(ceRNA)对癌症分子生物学机制的影响引起了极大的兴趣。在这项研究中,基于癌症基因组图谱(TCGA)数据库筛选和构建了长非编码 RNA-微小 RNA-信使 RNA(lncRNA-miRNA-mRNA)ceRNA 网络,并评估了其预测乳腺癌患者预后的功效。从 TCGA 数据库下载了 RNA 测序、miRNA 测序和相应的临床信息,在数据搜索后筛选出差异表达基因。通过加权相关网络分析(WGCNA)分析两组基因之间的相似性。接下来,预测 lncRNA、miRNA 和 mRNA 之间的相互作用,构建 lncRNA-miRNA-mRNA ceRNA 网络。最后,采用单因素和多因素 Cox 回归分析筛选预后因素,构建预后风险模型。使用受试者工作特征(ROC)曲线评估该模型预测乳腺癌患者预后的疗效。在乳腺癌组织中,共鉴定出 5056 个差异表达的 lncRNA、712 个差异表达的 miRNA 和 9878 个差异表达的 mRNA。WGCNA 预测 823 个 lncRNA 和 1813 个 mRNAs 与乳腺癌密切相关。基于 27 个 lncRNA、14 个 miRNA 和 4 个 mRNA 构建了乳腺癌相关的 lncRNA-miRNA-mRNA ceRNA 网络。ZC3H12B、HRH1、TMEM132C 和 PAG 是乳腺癌患者预后的可能独立危险因素,ROC 曲线下信号特征曲线的面积为 0.609。本研究表明,基于 ZC3H12B、HRH1、TMEM132C 和 PAG1 的预后风险模型能准确预测乳腺癌患者的预后。

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