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结直肠癌中lncRNA相关竞争性内源性RNA网络的构建及综合预后分析

The Construction and Comprehensive Prognostic Analysis of the LncRNA-Associated Competitive Endogenous RNAs Network in Colorectal Cancer.

作者信息

Li Wei, Yu Weifang, Jiang Xia, Gao Xian, Wang Guiqi, Jin Xiaojing, Zhao Zengren, Liu Yuegeng

机构信息

Department of General Surgery, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang, China.

Departments of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Front Genet. 2020 Jun 23;11:583. doi: 10.3389/fgene.2020.00583. eCollection 2020.

DOI:10.3389/fgene.2020.00583
PMID:32714366
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7344331/
Abstract

Competing endogenous RNAs (ceRNAs) are a newly proposed RNA interaction mechanism that has been associated with the tumorigenesis, metastasis, diagnosis, and predicting survival of various cancers. In this study, we constructed a ceRNA network in colorectal cancer (CRC). Then, we sought to develop and validate a composite clinicopathologic-genomic nomogram using The Cancer Genome Atlas (TCGA) database. To construct the ceRNA network in CRC, we analyzed the mRNAseq, miRNAseq data, and clinical information from TCGA database. LncRNA, miRNA, and mRNA signatures were identified to construct risk score as independent indicators of the prognostic value in CRC patients. A composite clinicopathologic-genomic nomogram was developed to predict the overall survival (OS). One hundred sixty-one CRC-specific lncRNAs, 97 miRNAs, and 161 mRNAs were identified to construct the ceRNA network. Multivariate Cox proportional hazards regression analysis indicated that nine-lncRNA signatures, eight-miRNA signatures, and five-mRNA signatures showed a significant prognostic value for CRC. Furthermore, a clinicopathologic-genomic nomogram was constructed in the primary cohort, which performed well in both the primary and validation sets. This study presents a nomogram that incorporates the CRC-specific ceRNA expression profile, clinical features, and pathological factors, which demonstrate its excellent differentiation and risk stratification in predicting OS in CRC patients.

摘要

竞争性内源性RNA(ceRNA)是一种新提出的RNA相互作用机制,与多种癌症的发生、转移、诊断及生存预测相关。在本研究中,我们构建了结直肠癌(CRC)的ceRNA网络。然后,我们试图利用癌症基因组图谱(TCGA)数据库开发并验证一个综合临床病理-基因组列线图。为构建CRC的ceRNA网络,我们分析了TCGA数据库中的mRNA测序、miRNA测序数据及临床信息。鉴定lncRNA、miRNA和mRNA特征以构建风险评分,作为CRC患者预后价值的独立指标。开发了一个综合临床病理-基因组列线图来预测总生存期(OS)。鉴定出161个CRC特异性lncRNA、97个miRNA和161个mRNA以构建ceRNA网络。多变量Cox比例风险回归分析表明,9个lncRNA特征、8个miRNA特征和5个mRNA特征对CRC具有显著的预后价值。此外,在主要队列中构建了一个临床病理-基因组列线图,其在主要数据集和验证数据集中均表现良好。本研究提出了一个纳入CRC特异性ceRNA表达谱、临床特征和病理因素的列线图,其在预测CRC患者的OS方面显示出优异的区分度和风险分层能力。

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