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用于预测肺鳞状细胞癌预后和免疫格局的N6-甲基腺苷(m6A)相关长链非编码RNA特征的鉴定

Identification of a N6-Methyladenosine (m6A)-Related lncRNA Signature for Predicting the Prognosis and Immune Landscape of Lung Squamous Cell Carcinoma.

作者信息

Weng Chengyin, Wang Lina, Liu Guolong, Guan Mingmei, Lu Lin

机构信息

Department of Medical Oncology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

出版信息

Front Oncol. 2021 Nov 18;11:763027. doi: 10.3389/fonc.2021.763027. eCollection 2021.

Abstract

BACKGROUND

m6A-related lncRNAs emerged as potential targets for tumor diagnosis and treatment. This study aimed to identify m6A-regulated lncRNAs in lung squamous cell carcinoma (LUSC) patients.

MATERIALS AND METHODS

RNA sequencing and the clinical data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The m6A-related lncRNAs were identified by using Pearson correlation assay. Univariate and multivariate Cox regression analyses were utilized to construct a risk model. The performance of the risk model was validated using Kaplan-Meier survival analysis and receiver operating characteristics (ROC). Immune estimation of LUSC was downloaded from TIMER, and the correlations between the risk score and various immune cells infiltration were analyzed using various methods. Differences in immune functions and expression of immune checkpoint inhibitors and m6A regulators between high-risk and low-risk groups were further explored. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to explore the biological functions of AL122125.1.

RESULTS

A total of 351 m6A-related lncRNAs were obtained from TCGA. Seven lncRNAs demonstrated prognostic values. A further multivariate Cox regression assay constructed a risk model consisting of two lncRNAs (AL122125.1 and HORMAD2-AS1). The Kaplan-Meier analysis and area under the curve indicated that this risk model could be used to predict the prognosis of LUSC patients. The m6A-related lncRNAs were immune-associated. There were significant correlations between risk score and immune cell infiltration, immune functions, and expression of immune checkpoint inhibitors. Meanwhile, there were significant differences in the expression of m6A regulators between the high- and low-risk groups. Moreover, GO and KEGG analyses revealed that the upregulated expression of AL122125.1 was tumor-related.

CONCLUSION

In this study, we constructed an m6A-related lncRNA risk model to predict the survival of LUSC patients. This study could provide a novel insight to the prognosis and treatment of LUSC patients.

摘要

背景

m6A相关的长链非编码RNA(lncRNA)成为肿瘤诊断和治疗的潜在靶点。本研究旨在鉴定肺鳞状细胞癌(LUSC)患者中m6A调控的lncRNA。

材料与方法

从癌症基因组图谱(TCGA)数据库下载LUSC患者的RNA测序数据和临床资料。采用Pearson相关分析鉴定m6A相关的lncRNA。利用单因素和多因素Cox回归分析构建风险模型。使用Kaplan-Meier生存分析和受试者工作特征(ROC)曲线验证风险模型的性能。从TIMER下载LUSC的免疫评估数据,并使用多种方法分析风险评分与各种免疫细胞浸润之间的相关性。进一步探讨高风险组和低风险组之间免疫功能、免疫检查点抑制剂和m6A调节因子表达的差异。最后,利用基因本体(GO)和京都基因与基因组百科全书(KEGG)分析来探索AL122125.1的生物学功能。

结果

从TCGA中总共获得了351个m6A相关的lncRNA。7个lncRNA具有预后价值。进一步的多因素Cox回归分析构建了一个由两个lncRNA(AL122125.1和HORMAD2-AS1)组成的风险模型。Kaplan-Meier分析和曲线下面积表明,该风险模型可用于预测LUSC患者的预后。m6A相关的lncRNA与免疫相关。风险评分与免疫细胞浸润、免疫功能以及免疫检查点抑制剂的表达之间存在显著相关性。同时,高风险组和低风险组之间m6A调节因子的表达存在显著差异。此外,GO和KEGG分析表明AL122125.1的上调表达与肿瘤相关。

结论

在本研究中,我们构建了一个m6A相关的lncRNA风险模型来预测LUSC患者的生存情况。本研究可为LUSC患者的预后和治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dc3/8637334/414e3dbe9d91/fonc-11-763027-g001.jpg

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