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基于TCGA数据的急性髓系白血病患者lncRNAs的DesA预后风险模型。

DesA Prognostic Risk Model of LncRNAs in Patients With Acute Myeloid Leukaemia Based on TCGA Data.

作者信息

Ding Weidong, Ling Yun, Shi Yuan, Zheng Zhuojun

机构信息

Department of Hematology, The Third Affiliated Hospital of Soochow University, Soochow, China.

Laboratory of Hematology, The Third Affiliated Hospital of Soochow University, Soochow, China.

出版信息

Front Bioeng Biotechnol. 2022 Feb 21;10:818905. doi: 10.3389/fbioe.2022.818905. eCollection 2022.

Abstract

This study aimed to combine the clinical data of acute myeloid leukaemia (AML) from The Cancer Genome Atlas (TCGA) database to obtain prognosis-related biomarkers, construct a prognostic risk model using long non-coding RNAs (lncRNAs) in AML and help patients with AML make clinical treatment decisions. We analysed the transcriptional group information of 151 patients with AML obtained from TCGA and extracted the expressions of lncRNAs. According to the mutation frequency, the patients were divided into the high mutation group (genomic unstable group, top 25% of mutation frequency) and low mutation group (genomic stable group, 25% after mutation frequency). The 'limma' R package was used to analyse the difference in lncRNA expressions between the two groups, and the "survival," "caret," and "glmnet" R packages were used to screen lncRNAs that are related to clinical prognosis. Subsequently, a prognosis-related risk model was constructed and verified through different methods. According to the lncRNA expression data in TCGA, we found that seven lncRNAs (i.e. AL645608.6, LINC01436, AL645608.2, AC073534.2, LINC02593, AL512413.1, and AL645608.4) were highly correlated with the clinical prognosis of patients with AML, so we constructed a prognostic risk model of lncRNAs based on LINC01436, AC073534.2, and LINC02593. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of differentially expressed lncRNA-related target genes were performed, receiver operating characteristic (ROC) curves were created, the applicability of the model in children was assessed using the TARGET database and the model was externally verified using the GEO database. Furthermore, different expression patterns of lncRNAs were validated in various AML cell lines derived from Homo sapiens. We have established a lncRNA prognostic model that can predict the survival of patients with AML. The Kaplan-Meier analysis showed that this model distinguished survival differences between patients with high- and low-risk status. The ROC analysis confirmed this finding and showed that the model had high prediction accuracy. The Kaplan-Meier analysis of the clinical subgroups showed that this model can predict prognosis independent of clinicopathological factors. Therefore, the proposed prognostic lncRNA risk model can be used as an independent biomarker of AML.

摘要

本研究旨在整合来自癌症基因组图谱(TCGA)数据库的急性髓系白血病(AML)临床数据,以获取与预后相关的生物标志物,利用AML中的长链非编码RNA(lncRNA)构建预后风险模型,并帮助AML患者做出临床治疗决策。我们分析了从TCGA获得的151例AML患者的转录组信息,并提取了lncRNA的表达情况。根据突变频率,将患者分为高突变组(基因组不稳定组,突变频率前25%)和低突变组(基因组稳定组,突变频率后25%)。使用“limma”R包分析两组之间lncRNA表达的差异,使用“survival”“caret”和“glmnet”R包筛选与临床预后相关的lncRNA。随后,构建了一个与预后相关的风险模型,并通过不同方法进行验证。根据TCGA中的lncRNA表达数据,我们发现7种lncRNA(即AL645608.6、LINC01436、AL645608.2、AC073534.2、LINC02593、AL512413.1和AL645608.4)与AML患者的临床预后高度相关,因此我们基于LINC01436、AC073534.2和LINC02593构建了lncRNA的预后风险模型。对差异表达的lncRNA相关靶基因进行了基因本体论和京都基因与基因组百科全书通路分析,绘制了受试者工作特征(ROC)曲线,使用TARGET数据库评估了该模型在儿童中的适用性,并使用GEO数据库进行了外部验证。此外,在源自智人的各种AML细胞系中验证了lncRNA的不同表达模式。我们建立了一个可以预测AML患者生存情况的lncRNA预后模型。Kaplan-Meier分析表明,该模型区分了高危和低危状态患者的生存差异。ROC分析证实了这一发现,并表明该模型具有较高的预测准确性。临床亚组的Kaplan-Meier分析表明,该模型可以独立于临床病理因素预测预后。因此,所提出的lncRNA预后风险模型可作为AML的独立生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d80/8899517/2d4769c13671/fbioe-10-818905-g001.jpg

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