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一种基于缺氧相关长链非编码RNA分子亚型的膀胱癌预后评估新模型。

A Novel Assessment Model Based on Molecular Subtypes of Hypoxia-Related LncRNAs for Prognosis of Bladder Cancer.

作者信息

Chen Xianwu, Zhang Yan, Wang Feifan, Zhou Xuejian, Fu Qinghe, Yang Xintao, Lin Juntao, Jin Xiaodong

机构信息

Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Front Cell Dev Biol. 2021 Nov 15;9:718991. doi: 10.3389/fcell.2021.718991. eCollection 2021.

Abstract

Hypoxia is a common feature in various tumors that regulates aggressiveness. Previous studies have demonstrated that some dysregulated long non-coding RNAs (lncRNAs) are correlated with tumor progression, including bladder cancer (BCa). However, the prognostic effect of hypoxia-related lncRNAs (HRLs) and their clinical relevance, as well as their regulatory effect on the tumor immune microenvironment, are largely unknown in BCa. A co-expression analysis between hypoxia genes and lncRNA expression, which was downloaded from the TCGA database, was performed to identify HRLs. Univariate Cox regression analysis was performed to select the most desirable lncRNAs for molecular subtype, and further LASSO analysis was performed to develop a prognostic model. This molecular subtype based on four HRLs (AC104653, AL136084, AL139393, and LINC00892) showed good performance in the tumor microenvironment and tumor mutation burden. The prognostic risk model suggested better performance in predicting BCa patients' prognosis and obtained a close correlation with clinicopathologic features. Furthermore, four of five first-line clinical chemotherapies showed different sensitivities to this model, and nine immune checkpoints showed different expression in the molecular subtypes or the risk model. In conclusion, this study indicates that this molecular subtype and risk model based on HRLs may be useful in improving the prognostic prediction of BCa patients with different clinical situations and may help to find a useful target for tumor therapy.

摘要

缺氧是各种肿瘤中调节侵袭性的常见特征。先前的研究表明,一些失调的长链非编码RNA(lncRNA)与肿瘤进展相关,包括膀胱癌(BCa)。然而,缺氧相关lncRNA(HRL)的预后作用及其临床相关性,以及它们对肿瘤免疫微环境的调节作用,在BCa中很大程度上尚不清楚。我们从TCGA数据库下载了缺氧基因与lncRNA表达之间的共表达分析,以鉴定HRL。进行单变量Cox回归分析以选择最适合分子亚型的lncRNA,并进一步进行LASSO分析以建立预后模型。这种基于四种HRL(AC104653、AL136084、AL139393和LINC00892)的分子亚型在肿瘤微环境和肿瘤突变负荷方面表现良好。预后风险模型在预测BCa患者的预后方面表现更好,并与临床病理特征密切相关。此外,五种一线临床化疗中的四种对该模型表现出不同的敏感性,九种免疫检查点在分子亚型或风险模型中表现出不同的表达。总之,本研究表明,这种基于HRL的分子亚型和风险模型可能有助于改善不同临床情况的BCa患者的预后预测,并可能有助于找到有用的肿瘤治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1802/8634255/91880b783383/fcell-09-718991-g001.jpg

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