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急性髓系白血病N6-甲基腺苷相关长链非编码RNA预后及免疫细胞浸润的综合分析

Comprehensive Analysis of N6-Methyladenosine-Related Long Noncoding RNA Prognosis of Acute Myeloid Leukemia and Immune Cell Infiltration.

作者信息

Zheng Guowei, Liu Mengying, Chang Xinyu, Cao Xiting, Dong Ani, Zhu Huili, Hu Wanli, Xie Junna, Zhao Yang, Hu Dongsheng, Jia Xiaocan, Yang Yongli, Shi Xuezhong, Lu Jie

机构信息

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.

College of Public Health, Zhengzhou University, Zhengzhou, China.

出版信息

Front Genet. 2022 May 4;13:888173. doi: 10.3389/fgene.2022.888173. eCollection 2022.

Abstract

N6-Methyladenosine-related long noncoding RNAs play an essential role in many cancers' development. However, the relationship between m6A-related lncRNAs and acute myelogenous leukemia (AML) prognosis remains unclear. We systematically analyzed the association of m6A-related lncRNAs with the prognosis and tumor immune microenvironment (TME) features using the therapeutically applicable research to generate effective treatment (TARGET) database. We screened 315 lncRNAs associated with AML prognosis and identified nine key lncRNAs associated with m6A by the LASSO Cox analysis. A model was established based on these nine lncRNAs and the predictive power was explored in The Cancer Genome Atlas (TCGA) database. The areas under the ROC curve of TARGET and TCGA databases for ROC at 1, 3, and 5 years are 0.701, 0.704, and 0.696, and 0.587, 0.639, and 0.685, respectively. The nomogram and decision curve analysis (DCA) showed that the risk score was more accurate than other clinical indicators in evaluating patients' prognoses. The clusters with a better prognosis enrich the AML pathways and immune-related pathways. We also found a close correlation between prognostic m6A-related lncRNAs and tumor immune cell infiltration. LAG3 expression at the immune checkpoint was lower in the worse prognostic cluster. In conclusion, m6A-related lncRNAs partly affected AML prognosis by remodeling the TME and affecting the anticarcinogenic ability of immune checkpoints, especially LAG3 inhibitors. The prognostic model constructed with nine key m6A-related lncRNAs can provide a method to assess the prognosis of AML patients in both adults and children.

摘要

N6-甲基腺苷相关的长链非编码RNA在多种癌症的发展中起着至关重要的作用。然而,m6A相关的长链非编码RNA与急性髓系白血病(AML)预后之间的关系仍不清楚。我们使用治疗应用研究生成有效治疗(TARGET)数据库,系统地分析了m6A相关的长链非编码RNA与预后及肿瘤免疫微环境(TME)特征之间的关联。我们筛选出315个与AML预后相关的长链非编码RNA,并通过LASSO Cox分析确定了9个与m6A相关的关键长链非编码RNA。基于这9个长链非编码RNA建立了一个模型,并在癌症基因组图谱(TCGA)数据库中探索了其预测能力。TARGET和TCGA数据库在1年、3年和5年时的ROC曲线下面积分别为0.701、0.704和0.696,以及0.587、0.639和0.685。列线图和决策曲线分析(DCA)表明,风险评分在评估患者预后方面比其他临床指标更准确。预后较好的聚类富集了AML通路和免疫相关通路。我们还发现预后相关的m6A长链非编码RNA与肿瘤免疫细胞浸润之间存在密切相关性。免疫检查点处LAG3的表达在预后较差的聚类中较低。总之,m6A相关的长链非编码RNA通过重塑TME和影响免疫检查点尤其是LAG3抑制剂的抗癌能力,部分影响了AML的预后。由9个关键的m6A相关长链非编码RNA构建的预后模型可为评估成人和儿童AML患者的预后提供一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/9115802/10268db3ba90/fgene-13-888173-g001.jpg

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