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基于N6-甲基腺苷相关长链非编码RNA构建软组织肉瘤的新型特征并预测免疫格局

Construction of a Novel Signature and Prediction of the Immune Landscape in Soft Tissue Sarcomas Based on N6-Methylandenosine-Related LncRNAs.

作者信息

Zhang Li, Tang Xianzhe, Wan Jia, Zhang Xianghong, Zheng Tao, Lin Zhengjun, Liu Tang

机构信息

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, China.

Department of Endocrinology, The Fifth Central Hospital of Tianjin, Tianjin, China.

出版信息

Front Mol Biosci. 2021 Oct 15;8:715764. doi: 10.3389/fmolb.2021.715764. eCollection 2021.

Abstract

N6-methylandenosine-related long non-coding RNAs (m6A-related lncRNAs) are critically involved in cancer development. However, the roles and clinical significance of m6A-related lncRNAs in soft tissue sarcomas (STS) are inconclusive, thereby warranting further investigations. Transcriptome profiling data were extracted from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). Consensus clustering was employed to divide patients into clusters and Kaplan-Meier analysis was used to explore the prognostic differences between the subgroups. Gene set enrichment analysis (GSEA) was conducted to identify the biological processes and signaling pathways associated with m6A-Related lncRNAs. Finally, patients were randomly divided into training and validation cohorts, and least absolute shrinkage and selection operator (LASSO) Cox regression was conducted to establish the m6A-related lncRNA-based risk signature. A total of 259 STS patients from TCGA-SARC dataset were enrolled in our study. Thirteen m6A-Related lncRNAs were identified to be closely related to the prognosis of STS patients. Patients were divided into two clusters, and patients in cluster 2 had a better overall survival (OS) than those in cluster 1. Patients in different clusters also showed differences in immune scores, infiltrating immune cells, and immune checkpoint expression. Patients were further classified into high-risk and low-risk subgroups according to risk scores, and high-risk patients were found to have a worse prognosis. The receiver operating characteristic (ROC) curve indicated that the risk signature displayed excellent performance at predicting the prognosis of patients with STS. Further, the risk signature was remarkably connected with the immune microenvironment and chemosensitivity in STS. Our study demonstrated that m6A-related lncRNAs were significantly associated with prognosis and tumor immune microenvironment and could function as independent prognosis-specific predictors in STS, thereby providing novel insights into the roles of m6A-related lncRNAs in STS.

摘要

N6-甲基腺苷相关的长链非编码RNA(m6A相关lncRNA)在癌症发展中起着关键作用。然而,m6A相关lncRNA在软组织肉瘤(STS)中的作用和临床意义尚无定论,因此有必要进一步研究。从癌症基因组图谱(TCGA)数据库和基因型-组织表达(GTEx)中提取转录组谱数据。采用一致性聚类将患者分为不同簇,并使用Kaplan-Meier分析探讨亚组之间的预后差异。进行基因集富集分析(GSEA)以确定与m6A相关lncRNA相关的生物学过程和信号通路。最后,将患者随机分为训练队列和验证队列,并进行最小绝对收缩和选择算子(LASSO)Cox回归以建立基于m6A相关lncRNA的风险特征。本研究纳入了来自TCGA-SARC数据集的259例STS患者。鉴定出13种m6A相关lncRNA与STS患者的预后密切相关。患者被分为两个簇,簇2中的患者总生存期(OS)比簇1中的患者更好。不同簇中的患者在免疫评分、免疫浸润细胞和免疫检查点表达方面也存在差异。根据风险评分将患者进一步分为高风险和低风险亚组,发现高风险患者预后较差。受试者工作特征(ROC)曲线表明,该风险特征在预测STS患者预后方面表现出色。此外,该风险特征与STS中的免疫微环境和化疗敏感性显著相关。我们的研究表明,m6A相关lncRNA与预后和肿瘤免疫微环境显著相关,并且可以作为STS中独立的预后特异性预测指标,从而为m6A相关lncRNA在STS中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbe8/8559337/f5400efc0c8f/fmolb-08-715764-g001.jpg

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