N6-Methyladenosine-Related lncRNAs Are Novel Prognostic Markers and Predict the Immune Landscape in Acute Myeloid Leukemia.
N6-Methyladenosine-Related lncRNAs Are Novel Prognostic Markers and Predict the Immune Landscape in Acute Myeloid Leukemia.
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N6-甲基腺苷相关 lncRNA 是新型预后标志物，可预测急性髓系白血病的免疫状况
DOI：
10.3389/fgene.2022.804614
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
背景：急性髓细胞白血病(AML)是预后不良的血液系统肿瘤之一。然而，N6-甲基腺苷相关的长非编码RNA(LncRNAs)在AML中的预后价值仍然难以捉摸。材料和方法：从癌症基因组图谱(TCGA)和基因表达总览(GEO)数据库中获取m6A相关基因的转录数据。根据m6A相关lncRNAs的表达将AML标本分为不同亚组。观察不同亚型AML在生物学功能、肿瘤免疫微环境、拷贝数变异(CNV)、药物敏感性等方面的差异。此外，还建立了与m6A相关的lncRNA预后模型来评估AML患者的预后。结果：选择9个与预后相关的m6A相关LncRNAs构建预后模型。通过Kaplan-Meier分析和随时间变化的受试者工作特征(ROC)曲线进一步确定模型的准确性。然后，根据风险分数的中位数将AML样本分为高风险组和低风险组。基因集浓缩分析(GSEA)表明，风险较高的样本具有异常的免疫相关生物学过程和信号通路。值得注意的是，高危人群与免疫评分和基质评分增加以及明显的免疫细胞渗透显著相关。此外，我们还发现，高危人群对多种化疗药物和小分子抗癌药物的IC50值较高，尤其是TW.37和MG.132。此外，还绘制了用于评估AML患者总体生存(OS)的诺模图。基于风险评分中位数的模型在预测预后和生存状态方面显示出可靠的准确性。结论：本研究根据M6A相关LncRNAs的表达建立了AML的预后风险模型。值得注意的是，该签名还可能作为一种新的生物标记物，可以指导临床应用，例如，选择可以从免疫治疗中受益的AML患者。
Background: Acute myelocytic leukemia (AML) is one of the hematopoietic cancers with an unfavorable prognosis. However, the prognostic value of N 6-methyladenosine-associated long non-coding RNAs (lncRNAs) in AML remains elusive. Materials and Methods: The transcriptomic data of m6A-related lncRNAs were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. AML samples were classified into various subgroups according to the expression of m6A-related lncRNAs. The differences in terms of biological function, tumor immune microenvironment, copy number variation (CNV), and drug sensitivity in AML between distinct subgroups were investigated. Moreover, an m6A-related lncRNA prognostic model was established to evaluate the prognosis of AML patients. Results: Nine prognosis-related m6A-associated lncRNAs were selected to construct a prognosis model. The accuracy of the model was further determined by the Kaplan–Meier analysis and time-dependent receiver operating characteristic (ROC) curve. Then, AML samples were classified into high- and low-risk groups according to the median value of risk scores. Gene set enrichment analysis (GSEA) demonstrated that samples with higher risks were featured with aberrant immune-related biological processes and signaling pathways. Notably, the high-risk group was significantly correlated with an increased ImmuneScore and StromalScore, and distinct immune cell infiltration. In addition, we discovered that the high-risk group harbored higher IC50 values of multiple chemotherapeutics and small-molecule anticancer drugs, especially TW.37 and MG.132. In addition, a nomogram was depicted to assess the overall survival (OS) of AML patients. The model based on the median value of risk scores revealed reliable accuracy in predicting the prognosis and survival status. Conclusion: The present research has originated a prognostic risk model for AML according to the expression of prognostic m6A-related lncRNAs. Notably, the signature might also serve as a novel biomarker that could guide clinical applications, for example, selecting AML patients who could benefit from immunotherapy.
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影响因子：
--
作者：
Li Z;Li Y;Zhong W;Huang P
通讯作者：
Huang P
影响因子：
3.6
作者：
Cai SF;Levine RL
通讯作者：
Levine RL
影响因子：
158.5
作者：
DiNardo, C. D.;Stein, E. M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
影响因子：
--
作者：
Li N;Chen X;Liu Y;Zhou T;Li W
通讯作者：
Li W
影响因子：
50.3
作者：
Dufva, Olli;Polonen, Petri;Mustjoki, Satu
通讯作者：
Mustjoki, Satu