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一种用于预测结肠癌预后和评估肿瘤免疫微环境的新型m7G相关lncRNA风险模型。

A novel m7G-related lncRNA risk model for predicting prognosis and evaluating the tumor immune microenvironment in colon carcinoma.

作者信息

Yang Sheng, Zhou Jiahui, Chen Zhihao, Sun Qingyang, Zhang Dongsheng, Feng Yifei, Wang Xiaowei, Sun Yueming

机构信息

First Clinical Medical College, Nanjing Medical University, Nanjing, China.

Department of General Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Front Oncol. 2022 Aug 4;12:934928. doi: 10.3389/fonc.2022.934928. eCollection 2022.

Abstract

N7-Methylguanosine (m7G) modifications are a common type of posttranscriptional RNA modifications. Its function in the tumor microenvironment (TME) has garnered widespread focus in the past few years. Long non-coding RNAs (lncRNAs) played an essential part in tumor development and are closely associated with the tumor immune microenvironment. In this study, we employed a comprehensive bioinformatics approach to develop an m7G-associated lncRNA prognostic model based on the colon adenocarcinoma (COAD) database from The Cancer Genome Atlas (TCGA) database. Pearson's correlation analysis was performed to identify m7G-related lncRNAs. Differential gene expression analysis was used to screen lncRNAs. Then, we gained 88 differentially expressed m7G-related lncRNAs. Univariate Cox analysis and Lasso regression analysis were performed to build an eight-m7G-related-lncRNA (ELFN1-AS1, GABPB1-AS1, SNHG7, GS1-124K5.4, ZEB1-AS1, PCAT6, C1RL-AS1, MCM3AP-AS1) risk model. Consensus clustering analysis was applied to identify the m7G-related lncRNA subtypes. We also verified the risk prediction effect of a gene signature in the GSE17536 test set (177 patients). A nomogram was constructed to predict overall survival rates. Furthermore, we analyzed differentially expressed genes (DEGs) between high-risk and low-risk groups. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted with the analyzed DEGs. At last, single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, MCP-COUNTER, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithms were utilized to discover the relationship between the risk model and the TME. Consequently, the m7G-related lncRNA risk model for COAD patients could be a viable prognostic tool and treatment target.

摘要

N7-甲基鸟苷(m7G)修饰是一种常见的转录后RNA修饰类型。在过去几年中,其在肿瘤微环境(TME)中的功能已受到广泛关注。长链非编码RNA(lncRNA)在肿瘤发展中起着重要作用,并且与肿瘤免疫微环境密切相关。在本研究中,我们采用综合生物信息学方法,基于来自癌症基因组图谱(TCGA)数据库的结肠腺癌(COAD)数据库开发了一种与m7G相关的lncRNA预后模型。进行Pearson相关性分析以鉴定与m7G相关的lncRNA。使用差异基因表达分析来筛选lncRNA。然后,我们获得了88个差异表达的与m7G相关的lncRNA。进行单因素Cox分析和Lasso回归分析以构建一个包含8个与m7G相关的lncRNA(ELFN1-AS1、GABPB1-AS1、SNHG7、GS1-124K5.4、ZEB1-AS1、PCAT6、C1RL-AS1、MCM3AP-AS1)的风险模型。应用一致性聚类分析来鉴定与m7G相关的lncRNA亚型。我们还在GSE17536测试集(177例患者)中验证了基因特征的风险预测效果。构建了一个列线图来预测总生存率。此外,我们分析了高风险组和低风险组之间的差异表达基因(DEG)。使用分析得到的DEG进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后,利用单样本基因集富集分析(ssGSEA)、CIBERSORT、MCP-COUNTER和使用表达数据估计恶性肿瘤组织中的基质和免疫细胞(ESTIMATE)算法来发现风险模型与TME之间的关系。因此,COAD患者的与m7G相关的lncRNA风险模型可能是一种可行的预后工具和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ffb/9386370/4c4acbd4a550/fonc-12-934928-g001.jpg

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