Zhang Lulu, Ke Wen, Hu Pin, Li Zhangzhi, Geng Wei, Guo Yigang, Song Bin, Jiang Hua, Zhang Xia, Wan Chucheng
Department of Hematology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Department of Osteology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Front Genet. 2022 May 9;13:804614. doi: 10.3389/fgene.2022.804614. eCollection 2022.
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. 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. 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. 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.
急性髓细胞白血病(AML)是一种预后不良的造血系统癌症。然而,N6-甲基腺苷相关长链非编码RNA(lncRNA)在AML中的预后价值仍不明确。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)收集了与m6A相关lncRNA的转录组数据。根据m6A相关lncRNA的表达将AML样本分为不同亚组。研究了不同亚组在AML生物学功能、肿瘤免疫微环境、拷贝数变异(CNV)和药物敏感性方面的差异。此外,建立了一个与m6A相关的lncRNA预后模型来评估AML患者的预后。选择9个与预后相关的m6A相关lncRNA构建预后模型。通过Kaplan-Meier分析和时间依赖性受试者工作特征(ROC)曲线进一步确定模型的准确性。然后,根据风险评分的中位数将AML样本分为高风险组和低风险组。基因集富集分析(GSEA)表明,高风险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,高风险组与免疫评分和基质评分增加以及不同的免疫细胞浸润显著相关。此外,我们发现高风险组对多种化疗药物和小分子抗癌药物具有更高的半数抑制浓度(IC50)值,尤其是TW.37和MG.132。此外,绘制了列线图以评估AML患者的总生存期(OS)。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。本研究根据预后性m6A相关lncRNA的表达建立了AML的预后风险模型。值得注意的是,该标志物还可作为一种新型生物标志物,指导临床应用,例如选择可能从免疫治疗中获益的AML患者。