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基于芯片和生物信息学分析构建多发性骨髓瘤预后相关长非编码 RNA-mRNA 网络。

Construction of a prognosis‑associated long noncoding RNA‑mRNA network for multiple myeloma based on microarray and bioinformatics analysis.

机构信息

Department of Rheumatology and Immunology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China.

Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, Guangdong 518040, P.R. China.

出版信息

Mol Med Rep. 2020 Mar;21(3):999-1010. doi: 10.3892/mmr.2020.10930. Epub 2020 Jan 13.

Abstract

At present, the association between prognosis‑associated long noncoding RNAs (lncRNAs) and mRNAs is yet to be reported in multiple myeloma (MM). The aim of the present study was to construct prognostic models with lncRNAs and mRNAs, and to map the interactions between these lncRNAs and mRNAs in MM. LncRNA and mRNA data from 559 patients with MM were acquired from the Genome Expression Omnibus (dataset GSE24080), and their prognostic values were calculated using the survival package in R. Multivariate Cox analysis was used on the top 20 most significant prognosis‑associated mRNAs and lncRNAs to develop prognostic signatures. The performances of these prognostic signatures were tested using the survivalROC package in R, which allows for time‑dependent receiver operator characteristic (ROC) curve estimation. Weighted correlation network analysis (WGCNA) was conducted to investigate the associations between lncRNAs and mRNAs, and a lncRNA‑mRNA network was constructed using Cytoscape software. Univariate Cox regression analysis identified 39 lncRNAs and 1,445 mRNAs that were significantly associated with event‑free survival of MM patients. The top 20 most significant survival‑associated lncRNAs and mRNAs were selected as candidates for analyzing independent MM prognostic factors. Both signatures could be used to separate patients into two groups with distinct outcomes. The areas under the ROC curves were 0.739 for the lncRNA signature and 0.732 for the mRNA signature. In the lncRNA‑mRNA network, a total of 143 mRNAs were positively or negatively associated with 23 prognosis‑associated lncRNAs. NCRNA00201, LOC115110 and RP5‑968J1.1 were the most dominant drivers. The present study constructed a model that predicted prognosis in MM and formed a network with the corresponding prognosis‑associated mRNAs, providing a novel perspective for the clinical diagnosis and treatment of MM, and suggesting novel directions for interpreting the mechanisms underlying the development of MM.

摘要

目前,多发性骨髓瘤(MM)中预后相关长链非编码 RNA(lncRNA)与 mRNAs 之间的关联尚未见报道。本研究旨在构建具有 lncRNA 和 mRNAs 的预后模型,并绘制 MM 中这些 lncRNA 与 mRNAs 之间的相互作用图。从基因组表达综合数据库(数据集 GSE24080)中获取 559 例 MM 患者的 lncRNA 和 mRNA 数据,并使用 R 中的 survival 包计算其预后值。使用 R 中的 survivalROC 包对前 20 个最显著的预后相关 mRNAs 和 lncRNAs 进行多变量 Cox 分析,以开发预后特征。使用 R 中的 survivalROC 包测试这些预后特征的性能,该包允许进行时间依赖性接收者操作特征(ROC)曲线估计。加权相关网络分析(WGCNA)用于研究 lncRNA 与 mRNAs 之间的关联,并使用 Cytoscape 软件构建 lncRNA-mRNA 网络。单变量 Cox 回归分析确定了 39 个 lncRNA 和 1445 个与 MM 患者无事件生存显著相关的 mRNAs。选择前 20 个最显著的与生存相关的 lncRNA 和 mRNAs 作为分析独立 MM 预后因素的候选者。这两个特征都可以将患者分为两组,具有不同的结局。ROC 曲线下面积分别为 lncRNA 特征 0.739 和 mRNA 特征 0.732。在 lncRNA-mRNA 网络中,共有 143 个 mRNAs 与 23 个与预后相关的 lncRNA 呈正相关或负相关。NCRNA00201、LOC115110 和 RP5-968J1.1 是最主要的驱动因素。本研究构建了一个预测 MM 预后的模型,并与相应的预后相关 mRNAs 形成了一个网络,为 MM 的临床诊断和治疗提供了新的视角,并为解释 MM 发生发展的机制提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5069/7003030/26a0b368038d/MMR-21-03-0999-g00.jpg

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