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结肠腺癌中RNA结合蛋白的功能及预后价值的系统分析

Systematic analysis of the function and prognostic value of RNA binding proteins in Colon Adenocarcinoma.

作者信息

Qi Xuewei, Liu Zeyu, Zhang Qiaoli, Yang Ming, Wan Yuxiang, Huang Jinchang, Xu Lin

机构信息

Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing 100029, China.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.

出版信息

J Cancer. 2021 Mar 5;12(9):2537-2549. doi: 10.7150/jca.50407. eCollection 2021.

Abstract

Abnormal expression of RNA-binding proteins (RBPs) is closely related to tumorigenesis, progression, and prognosis. This study performed systematic bioinformatic analysis of RBPs abnormally expressed in colon adenocarcinoma (COAD) using the Cancer Genome Atlas (TCGA) database to screen prognostic markers and potential therapeutic targets. First, the gene expression data from COAD samples were used to screen out differentially expressed RBPs for functional enrichment analysis and to visualize interaction relationships. Second, RBPs that were significantly related to prognosis were screened through univariate and multivariate Cox regression analysis to construct a prognostic model. The prediction performance of the prognostic model was evaluated by survival analysis and receiver operating characteristic (ROC) curve analysis. It addition, it was verified in the test cohort. The Human Protein Atlas (HPA) online database was used to verify the expression levels of RBPs in the prognostic model. The study identified 181 differentially expressed RBPs and analyzed their interaction and functional enrichment, which were mainly related to non-coding RNA processing, ribosome biogenesis, RNA metabolic processes, RNA phosphodiester bond hydrolysis, and alternative mRNA splicing. Five RBPs related to prognosis were used to construct a prognostic model, and its predictive ability was verified by the test cohort. ROC curve analysis showed that the prognostic model had good sensitivity and specificity. Independent prognostic analysis showed that risk scores could be used as independent prognostic factors for COAD. This study constructed a reliable prognostic model by analyzing COAD differentially expressed RBPs, facilitating the screening of COAD prognostic markers and therapeutic targets.

摘要

RNA结合蛋白(RBPs)的异常表达与肿瘤发生、发展及预后密切相关。本研究利用癌症基因组图谱(TCGA)数据库对结肠腺癌(COAD)中异常表达的RBPs进行系统的生物信息学分析,以筛选预后标志物和潜在的治疗靶点。首先,利用COAD样本的基因表达数据筛选出差异表达的RBPs,进行功能富集分析并可视化相互作用关系。其次,通过单因素和多因素Cox回归分析筛选出与预后显著相关的RBPs,构建预后模型。通过生存分析和受试者工作特征(ROC)曲线分析评估预后模型的预测性能。此外,在测试队列中进行了验证。利用人类蛋白质图谱(HPA)在线数据库验证预后模型中RBPs的表达水平。该研究鉴定出181个差异表达的RBPs,并分析了它们的相互作用和功能富集情况,这些主要与非编码RNA加工、核糖体生物发生、RNA代谢过程、RNA磷酸二酯键水解和可变mRNA剪接有关。使用5个与预后相关的RBPs构建预后模型,并通过测试队列验证其预测能力。ROC曲线分析表明,该预后模型具有良好的敏感性和特异性。独立预后分析表明,风险评分可作为COAD的独立预后因素。本研究通过分析COAD差异表达的RBPs构建了可靠的预后模型,有助于筛选COAD的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f62e/8040719/0fa460db02c2/jcav12p2537g001.jpg

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