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基于代谢相关长链非编码RNA的膀胱癌预后模型

A Prognostic Model of Bladder Cancer Based on Metabolism-Related Long Non-Coding RNAs.

作者信息

Hu Jintao, Lai Cong, Shen Zefeng, Yu Hao, Lin Junyi, Xie Weibin, Su Huabin, Kong Jianqiu, Han Jinli

机构信息

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Guangdong Provincial Clinical Research Center for Urological Diseases, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Front Oncol. 2022 Feb 25;12:833763. doi: 10.3389/fonc.2022.833763. eCollection 2022.

Abstract

BACKGROUND

Some studies have revealed a close relationship between metabolism-related genes and the prognosis of bladder cancer. However, the relationship between metabolism-related long non-coding RNAs (lncRNA) regulating the expression of genetic material and bladder cancer is still blank. From this, we developed and validated a prognostic model based on metabolism-associated lncRNA to analyze the prognosis of bladder cancer.

METHODS

Gene expression, lncRNA sequencing data, and related clinical information were extracted from The Cancer Genome Atlas (TCGA). And we downloaded metabolism-related gene sets from the human metabolism database. Differential expression analysis is used to screen differentially expressed metabolism-related genes and lncRNAs between tumors and paracancer tissues. We then obtained metabolism-related lncRNAs associated with prognosis by correlational analyses, univariate Cox analysis, and logistic least absolute shrinkage and selection operator (LASSO) regression. A risk scoring model is constructed based on the regression coefficient corresponding to lncRNA calculated by multivariate Cox analysis. According to the median risk score, patients were divided into a high-risk group and a low-risk group. Then, we developed and evaluated a nomogram including risk scores and Clinical baseline data to predict the prognosis. Furthermore, we performed gene-set enrichment analysis (GSEA) to explore the role of these metabolism-related lncRNAs in the prognosis of bladder cancer.

RESULTS

By analyzing the extracted data, our research screened out 12 metabolism-related lncRNAs. There are significant differences in survival between high and low-risk groups divided by the median risk scoring model, and the low-risk group has a more favorable prognosis than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk score was closely related to the prognosis of bladder cancer. Then we established a nomogram based on multivariate analysis. After evaluation, the modified model has good predictive efficiency and clinical application value. Furthermore, the GSEA showed that these lncRNAs affected bladder cancer prognosis through multiple links.

CONCLUSIONS

A predictive model was established and validated based on 12 metabolism-related lncRNAs and clinical information, and we found these lncRNA affected bladder cancer prognosis through multiple links.

摘要

背景

一些研究揭示了代谢相关基因与膀胱癌预后之间的密切关系。然而,调节遗传物质表达的代谢相关长链非编码RNA(lncRNA)与膀胱癌之间的关系仍属空白。据此,我们开发并验证了一种基于代谢相关lncRNA的预后模型,以分析膀胱癌的预后情况。

方法

从癌症基因组图谱(TCGA)中提取基因表达、lncRNA测序数据及相关临床信息。我们还从人类代谢数据库下载了代谢相关基因集。采用差异表达分析筛选肿瘤组织与癌旁组织之间差异表达的代谢相关基因和lncRNA。然后,通过相关性分析、单因素Cox分析以及逻辑最小绝对收缩和选择算子(LASSO)回归,获得与预后相关的代谢相关lncRNA。基于多因素Cox分析计算出的lncRNA对应的回归系数构建风险评分模型。根据中位风险评分,将患者分为高风险组和低风险组。随后,我们开发并评估了一个包含风险评分和临床基线数据的列线图,以预测预后。此外,我们进行了基因集富集分析(GSEA),以探究这些代谢相关lncRNA在膀胱癌预后中的作用。

结果

通过对提取的数据进行分析,我们的研究筛选出了12个代谢相关lncRNA。由中位风险评分模型划分的高风险组和低风险组在生存率方面存在显著差异,且低风险组的预后比高风险组更优。单因素和多因素Cox回归分析表明,风险评分与膀胱癌预后密切相关。然后我们基于多因素分析建立了列线图。经评估,改进后的模型具有良好的预测效率和临床应用价值。此外,GSEA显示这些lncRNA通过多个环节影响膀胱癌预后。

结论

基于12个代谢相关lncRNA和临床信息建立并验证了一个预测模型,且我们发现这些lncRNA通过多个环节影响膀胱癌预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/179e/8913725/59c1ee72f559/fonc-12-833763-g001.jpg

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