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基于生物信息学分析构建预测头颈部鳞状细胞癌患者预后的铁死亡相关长非编码 RNA 标志物。

Constructing a Ferroptosis-related Long Non-coding RNA Signature to Predict the Prognostic of Head and Neck Squamous Cell Carcinoma Patients by Bioinformatic Analysis.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, 430071, People's Republic of China.

出版信息

Biochem Genet. 2022 Oct;60(5):1825-1844. doi: 10.1007/s10528-021-10176-2. Epub 2022 Jan 31.

Abstract

Ferroptosis is a novel discovered iron-dependent mode of regulated cell death (RCD) which characterized non-apoptosis. Researches have shown the effect of ferroptosis in the biological activities of tumors. But there is no relevant study showing the relationship between ferroptosis-related genes and head and neck squamous cell carcinoma (HNSCC). In this study, we paid attention to several ferroptosis-related lncRNAs in head and neck squamous cell carcinoma and its clinical features. HNSCC data were obtained from The Cancer Genome Atlas (TCGA) database. Ferroptosis-related lncRNAs were selected by the coexpression network. Then, we identified prognostic ferroptosis-related lncRNAs in HNSCC patients and constructed a ferroptosis-related lncRNAs signature by Lasso cox regression. Besides, GSEA analysis was performed to explore the functional enrichment of ferroptosis-related lncRNAs. Nine ferroptosis-related lncRNAs (AC004687.1, AL450992.2, AC010894.2, AL451085.2, AC104083.1, LIPE-AS1, AC108010.1, CTBP1-DT, and PTCSC2) were identified to have the independent prognostic value in HNSCC patients and the ferroptosis-related lncRNAs signature was constructed based on these nine genes. According to the risk score of the signature, the high-risk group had shorter overall survival (OS) compared with the low-risk group. Risk score showed to be an independent factor for the patients with HNSCC. Additionally, the nomogram was generated and the nine lncRNAs were mainly enriched in phagocytosis, metabolism, and chemokine signaling pathways. The ferroptosis-related lncRNA signature has effects on the prognostic prediction of patients with HNSCC which may serve as potential therapeutic targets for patients with HNSCC.

摘要

铁死亡是一种新发现的、依赖于铁的调控细胞死亡(RCD)模式,其特征是非凋亡性的。研究表明铁死亡在肿瘤的生物学活性中具有重要作用。但是,目前还没有相关研究表明铁死亡相关基因与头颈部鳞状细胞癌(HNSCC)之间的关系。在本研究中,我们关注了几种与头颈部鳞状细胞癌及其临床特征相关的铁死亡相关长链非编码 RNA(lncRNA)。HNSCC 数据从癌症基因组图谱(TCGA)数据库中获得。通过共表达网络筛选铁死亡相关 lncRNA。然后,我们鉴定了 HNSCC 患者中与铁死亡相关的预后 lncRNA,并通过 Lasso cox 回归构建了铁死亡相关 lncRNA 特征。此外,还进行了 GSEA 分析以探讨铁死亡相关 lncRNA 的功能富集。鉴定出 9 个铁死亡相关 lncRNA(AC004687.1、AL450992.2、AC010894.2、AL451085.2、AC104083.1、LIPE-AS1、AC108010.1、CTBP1-DT 和 PTCSC2)具有独立的预后价值,基于这 9 个基因构建了铁死亡相关 lncRNA 特征。根据特征的风险评分,高风险组的总生存期(OS)明显短于低风险组。风险评分是 HNSCC 患者的独立预后因素。此外,生成了列线图,这 9 个 lncRNA 主要富集在吞噬作用、代谢和趋化因子信号通路中。铁死亡相关 lncRNA 特征对头颈部鳞状细胞癌患者的预后预测具有影响,可能成为头颈部鳞状细胞癌患者潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6adb/9470613/6d3258025866/10528_2021_10176_Fig1_HTML.jpg

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