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基于 ceRNA 网络的儿童肾横纹肌肉瘤预后相关长非编码 RNA(lncRNA)潜在生物标志物的鉴定。

Identification of Potential Biomarkers of Prognosis-Related Long Non-Coding RNA (lncRNA) in Pediatric Rhabdoid Tumor of the Kidney Based on ceRNA Networks.

机构信息

Department of Pediatric Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland).

Shandong Key Laboratory of Digital Medicine and Computer Assisted Surgery, Qingdao, Shandong, China (mainland).

出版信息

Med Sci Monit. 2020 Dec 17;26:e927725. doi: 10.12659/MSM.927725.

Abstract

BACKGROUND Long non-coding RNA (lncRNA) can act as competing endogenous RNA (ceRNA) during tumor development. However, no study has elucidated the ceRNA network in pediatric rhabdoid tumor of the kidney (RTK) and its prognostic-related lncRNAs. The goal of the present study was to identify potential biomarkers of prognostic-related lncRNAs. MATERIAL AND METHODS RNA sequencing and clinical data were procured from the TARGET database. The "EdgeR" package was used to obtain differentially expressed lncRNA (DElncRNA), differentially expressed messenger RNAs (DEmRNA), and differentially expressed microRNAs (DEmiRNA). Cytoscape software was used to construct a ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted on the ceRNA network-related DEmRNA. The Kaplan-Meier method was used for predicting survival with ceRNA network-related DElncRNA. Univariate and multivariate Cox analyses were used to identify prognosis-related lncRNAs in the ceRNA network, and an RTK prognostic signature was constructed. RESULTS We identified 1109 DElncRNAs, 215 DEmiRNAs, and 3436 DEmRNAs; and 107 DElncRNAs, 21 DEmiRNAs, and 74 DEmRNAs were included in the ceRNA regulatory network. GO enrichment analysis and KEGG pathway enrichment indicated that the DEmRNAs were mainly related to the regulation of phospholipase C activity and the MAPK signaling pathway. Survival analysis showed that 9 of 107 DElncRNAs were correlated with prognosis (P<0.05). Univariate and multivariate Cox analysis identified 4 DElncRNAs (HNF1A-AS1, TPTEP1, SNHG6, and ZNF503-AS2) to establish a predictive model and can be used as independent prognostic biomarkers. CONCLUSIONS We constructed a ceRNA network that reveals potential lncRNA biomarkers for pediatric RTK.

摘要

背景

长非编码 RNA(lncRNA)在肿瘤发展过程中可以作为竞争内源性 RNA(ceRNA)发挥作用。然而,目前尚无研究阐明儿童肾横纹肌样瘤(RTK)的 ceRNA 网络及其与预后相关的 lncRNA。本研究旨在确定与预后相关的 lncRNA 的潜在生物标志物。

材料和方法

从 TARGET 数据库中获取 RNA 测序和临床数据。使用“EdgeR”软件包获取差异表达的 lncRNA(DElncRNA)、差异表达的信使 RNA(DEmRNA)和差异表达的 microRNA(DEmiRNA)。使用 Cytoscape 软件构建 ceRNA 网络。对 ceRNA 网络相关的 DEmRNA 进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用 Kaplan-Meier 方法预测 ceRNA 网络相关 DElncRNA 的生存情况。使用单变量和多变量 Cox 分析鉴定 ceRNA 网络中与预后相关的 lncRNA,并构建 RTK 预后特征。

结果

我们鉴定出 1109 个 DElncRNA、215 个 DEmiRNA 和 3436 个 DEmRNA;并纳入了 107 个 DElncRNA、21 个 DEmiRNA 和 74 个 DEmRNA 的 ceRNA 调控网络。GO 富集分析和 KEGG 通路富集分析表明,DEmRNAs 主要与磷脂酶 C 活性调节和 MAPK 信号通路相关。生存分析显示,107 个 DElncRNA 中有 9 个与预后相关(P<0.05)。单变量和多变量 Cox 分析确定了 4 个 DElncRNA(HNF1A-AS1、TPTEP1、SNHG6 和 ZNF503-AS2)来建立预测模型,并可作为独立的预后生物标志物。

结论

我们构建了一个 ceRNA 网络,揭示了儿童 RTK 的潜在 lncRNA 生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eaf/7754694/74e5edfc6cb9/medscimonit-26-e927725-g001.jpg

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