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全面描绘膀胱癌中与细胞坏死性凋亡相关的 lncRNAs,鉴定出用于预后预测的新型标志物。

Comprehensive Characterization of Necroptosis-Related lncRNAs in Bladder Cancer Identifies a Novel Signature for Prognosis Prediction.

机构信息

Department of Urology, Shenshan Medical Center, Memorial Hospital of Sun Yat-sen University, Shanwei, Guangdong, China.

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

出版信息

Dis Markers. 2022 Jun 6;2022:2360299. doi: 10.1155/2022/2360299. eCollection 2022.

Abstract

BACKGROUND

Bladder cancer (BC) is one of the most serious genitourinary malignant diseases with a poor prognosis. Necroptosis is a regulated form of cell death, and targeting necroptosis is emerging as a potential tumor therapy strategy. Nevertheless, the roles of necroptosis-related long noncoding RNAs (nrlncRNAs) in BC remains to be illustrated. This work is aimed at studying the clinical implications of nrlncRNAs in BC.

METHODS

The RNA-seq data and corresponding clinical data, downloaded from The Cancer Genome Atlas (TCGA) database, were utilized to obtain prognostic nrlncRNAs and construct a prediction nomogram for BC. The comprehensive profiling of the functional pathways, immune status, mutational landscape, and drug sensitivity related to the necroptosis-related lncRNA signature (NerRLsig) was performed.

RESULTS

Herein, a signature consisting of 12 necroptosis-related lncRNAs (AC015802.4, AL391807.1, AL078644.1, AC023825.2, AL132655.2, AP003352.1, STAG3L5P-PVRIG2P-PILRB, AC024451.4, MAP3K14-AS1, AL731567.1, AC010542.5, and AC009299.2) was constructed. The established signature can independently predict the poor overall survival of BC patients. Additionally, the NerRLsig had higher diagnostic validity compared to other clinicopathological variables, with a greater area under the receptor operating characteristic and concordance index curves. Finally, we found the differences in the functional signaling pathway, immune status, mutational profile, and drug sensitivity between the two subgroups.

CONCLUSION

This research revealed that the prognostic NerRLsig and nomogram could accurately predict the prognosis of BC.

摘要

背景

膀胱癌(BC)是预后最差的严重泌尿生殖系统恶性肿瘤之一。细胞程序性坏死是一种受调控的细胞死亡方式,靶向细胞程序性坏死已成为一种有潜力的肿瘤治疗策略。然而,细胞程序性坏死相关长链非编码 RNA(lncRNA)在 BC 中的作用仍有待阐明。本研究旨在探讨 lncRNA 与 BC 临床意义的相关性。

方法

从癌症基因组图谱(TCGA)数据库中下载 RNA-seq 数据和相应的临床数据,以获得与 BC 相关的预后 lncRNA,并构建用于 BC 的预测列线图。对与细胞程序性坏死相关 lncRNA 特征(NerRLsig)相关的功能途径、免疫状态、突变景观和药物敏感性进行综合分析。

结果

在此构建了一个由 12 个细胞程序性坏死相关 lncRNA(AC015802.4、AL391807.1、AL078644.1、AC023825.2、AL132655.2、AP003352.1、STAG3L5P-PVRIG2P-PILRB、AC024451.4、MAP3K14-AS1、AL731567.1、AC010542.5 和 AC009299.2)组成的特征。建立的特征可以独立预测 BC 患者的总体生存不良。此外,与其他临床病理变量相比,NerRLsig 具有更高的诊断准确性,受体工作特征曲线和一致性指数曲线下面积更大。最后,我们发现两个亚组之间在功能信号通路、免疫状态、突变特征和药物敏感性方面存在差异。

结论

本研究揭示了预后 NerRLsig 和列线图可准确预测 BC 的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/63d6/9194958/da130ea568e1/DM2022-2360299.001.jpg

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