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鉴定五个长非编码 RNA 标志物及构建膀胱癌预后风险评分模型。

Identification of five long noncoding RNAs signature and risk score for prognosis of bladder urothelial carcinoma.

机构信息

Department of Urinary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Department of Medical Oncology, Gaozhou People's Hospital, Gaozhou, China.

出版信息

J Cell Biochem. 2020 Jan;121(1):856-866. doi: 10.1002/jcb.29330. Epub 2019 Aug 2.

DOI:10.1002/jcb.29330
PMID:31373406
Abstract

Nowadays, an increasing number of studies illustrated that bladder urothelial cancer (BLCA) may act as the most common subtype of urological malignancies with a high rate of recurrence and metastasis. In this study, we attempted to establish a prognostic model and identify the possible pathway crosstalk. Long noncoding RNAs (lncRNAs) and mRNA expression and corresponding clinical information of patients with BLCA were downloaded from The Cancer Genome Atlas (TCGA). The differentially expressed genes analysis, univariate Cox analysis, the least absolute shrinkage, and selection operator Cox (LASSO Cox) regression model were then applied to identify five crucial lncRNAs (AC092725.1, AC104071.1, AL023584.1, AL132642.1, and AL137804.1). The multivariate cox analysis was utilized to calculate the regression coefficients (β ). The risk-score model was subsequently constructed as follows: (0.13541AC092725.1) + (0.20968AC104071.1) + (0.1525AL023584.1) - (0.14768AL132642.1) + (0.14387AL137804.1). Nomogram and assessment of overall survival (OS) prediction were verificated by the receiver operating characteristic curve in the testing group. As to 3-, 5-year OS prediction, the area under curve (AUC) for the nomogram of training data set was 0.83 and 0.86. Besides, the AUC (0.883 and 0.879) presented excellent predictive power in the testing group. In addition, the calibration plots validated the predictive performance of the nomogram. Weighted correlation network analysis (WGCNA) coupled with functional enrichment analysis contributed to explore the potential pathways, including PI3K-Akt, HIF-1, and Jak-STAT signaling pathways. Construction of the risk-score model and data analysis were both derived from multiple packages on the basis of the R platform chiefly.

摘要

如今,越来越多的研究表明,膀胱癌(BLCA)可能是泌尿系统最常见的恶性肿瘤亚型,其复发和转移率较高。本研究试图建立一个预后模型,并确定可能的途径相互作用。从癌症基因组图谱(TCGA)下载了膀胱癌患者的长链非编码 RNA(lncRNA)和 mRNA 表达及相应的临床信息。然后进行差异表达基因分析、单因素 Cox 分析、最小绝对收缩和选择算子 Cox(LASSO Cox)回归模型,以确定五个关键的 lncRNA(AC092725.1、AC104071.1、AL023584.1、AL132642.1 和 AL137804.1)。多因素 Cox 分析用于计算回归系数(β)。然后构建风险评分模型如下:(0.13541AC092725.1)+(0.20968AC104071.1)+(0.1525AL023584.1)-(0.14768AL132642.1)+(0.14387AL137804.1)。在测试组中,通过接受者操作特征曲线验证了列线图和总体生存(OS)预测的评估。对于 3 年和 5 年 OS 预测,训练数据集列线图的曲线下面积(AUC)分别为 0.83 和 0.86。此外,测试组的 AUC(0.883 和 0.879)表现出优异的预测能力。此外,校准图验证了列线图的预测性能。加权相关网络分析(WGCNA)结合功能富集分析有助于探索潜在途径,包括 PI3K-Akt、HIF-1 和 Jak-STAT 信号通路。风险评分模型的构建和数据分析主要基于 R 平台上的多个软件包。

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