基于单细胞和批量RNA测序联合分析构建急性髓细胞白血病新型炎症相关预后特征

Construction of a novel inflammatory-related prognostic signature of acute myelocytic leukemia based on conjoint analysis of single-cell and bulk RNA sequencing.

作者信息

Huang Yongfen, Yi Ping, Wang Yixuan, Wang Lingling, Cao Yongqin, Lu Jingbo, Fang Kun, Cheng Yuexin, Miao Yuqing

机构信息

Department of Hematology, Yancheng No.1 People's Hospital, Yancheng, China.

Department of Scientific Research Project, Wuhan Kindstar Medical Laboratory Co., Ltd., Wuhan, China.

出版信息

Front Immunol. 2025 Jun 10;16:1565954. doi: 10.3389/fimmu.2025.1565954. eCollection 2025.

Abstract

INTRODUCTION

The prognostic management of acute myeloid leukemia (AML) remains a challenge for clinicians. This study aims to construct a novel risk model for AML patient through comprehensive analysis of scRNA and bulk RNA data to optimize the precise treatment strategies for patients and improve prognosis.

METHODS AND RESULTS

scRNA-seq classified cells into nine clusters, including Bcells, erythrocyte, granulocyte-macrophage progenitor (GMP), hematopoietic stem cell progenitors (HSC/Prog), monocyte/macrophagocyte (Mono/Macro), myelocyte, neutrophils, plasma, and T/NK cells. Functional analysis demonstrated the important role of inflammation immune response in the pathogenesis of AML, and the leukocyte transendothelial migration and adhesion in the process of inflammation should be noticed. ssGSEA method identified four core cells including GMP, HSC/Prog, Mono/Macro, and myelocyte for subsequent analysis, which contains 1,594 marker genes. Furthermore, we identified AML-associated genes (2,067genes) and DEGs (1,010genes) between AML patients and controls usingGSE114868dataset. After performing intersection, univariate Cox, and LASSO analysis, we obtained a prognostic model based on the expression levels of five signature genes, namely, CALR, KDM1A, SUCNR1, TMEM220, and ADM. The prognostic model was then validated by two external datasets. Patients with high-risk scores are predisposed to experience poor overall survival. Further GSEA analysis of risk-model-related genes revealed the significant differences in inflammatory response between high-and low-risk groups.

CONCLUSION

In conclusion, we constructed an inflammation related risk model using internal scRNA data and external bulk RNA data, which can accurately distinguish survival outcomes in AML patients.

摘要

引言

急性髓系白血病(AML)的预后管理对临床医生来说仍然是一项挑战。本研究旨在通过对单细胞RNA(scRNA)和批量RNA数据进行综合分析,构建一种针对AML患者的新型风险模型,以优化患者的精准治疗策略并改善预后。

方法与结果

scRNA测序将细胞分为九个簇,包括B细胞、红细胞、粒-巨噬细胞祖细胞(GMP)、造血干细胞祖细胞(HSC/Prog)、单核细胞/巨噬细胞(Mono/Macro)、髓细胞、中性粒细胞、浆细胞和T/NK细胞。功能分析表明炎症免疫反应在AML发病机制中的重要作用,并且应注意炎症过程中的白细胞跨内皮迁移和黏附。单样本基因集富集分析(ssGSEA)方法确定了包括GMP、HSC/Prog、Mono/Macro和髓细胞在内的四个核心细胞用于后续分析,其中包含1594个标记基因。此外,我们使用GSE114868数据集鉴定了AML患者与对照组之间的AML相关基因(2067个基因)和差异表达基因(DEGs,1010个基因)。在进行交集、单变量Cox和套索分析后,我们基于五个特征基因(即CALR、KDM1A、SUCNR1、TMEM220和ADM)的表达水平获得了一个预后模型。然后通过两个外部数据集对该预后模型进行了验证。高风险评分的患者总体生存率较差。对风险模型相关基因的进一步基因集富集分析(GSEA)显示高风险组和低风险组之间在炎症反应方面存在显著差异。

结论

总之,我们使用内部scRNA数据和外部批量RNA数据构建了一个炎症相关风险模型,该模型可以准确区分AML患者的生存结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9372/12185455/ea6e3588e5cc/fimmu-16-1565954-g001.jpg

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