Liu Qiong, Zhou Zhaona, Xu Ping, Li Shuoye, Bu Xiuli, Zhang Jian, Guo Jun
Department of Hematology, Rizhao People's Hospital, No. 126 Tai'an Road, Rizhao, Shandong, 276800, China.
Department of Medical Imaging, Rizhao People's Hospital, No. 126 Tai'an Road, Rizhao, Shandong, 276800, China.
Cancer Cell Int. 2025 Apr 13;25(1):143. doi: 10.1186/s12935-025-03779-x.
Acute myeloid leukemia (AML) is a hematological malignancy characterized by complex immune microenvironment. This study aims to identify immune-related prognostic biomarkers in AML.
Multiple public sequencing datasets were utilized to analyze differentially expressed genes (DEGs) in AML. Single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were also performed. Immune cell infiltration was assessed at the single-cell level. NKT cell marker genes were intersected with the most AML-relevant module genes to identify key genes. Prognostic genes were screened using the Cox Lasso regression model, and their prognostic value was evaluated with Cox random forest and Kaplan-Meier survival analyses. Gene expression was validated using RT-qPCR and Western blot, and immune cell levels were analyzed by flow cytometry.
A total of 1,919 common DEGs were obtained between AML and controls. WGCNA revealed that the brown module was most strongly associated with AML. Single-cell analysis showed that NKT cell infiltration was significantly reduced in AML patients, consistent with ssGSEA results. Forty intersecting genes were identified between NKT cell marker genes and brown module genes. Cox Lasso regression identified 10 prognostic genes (FGFBP2, GZMB, GZMH, IKZF3, IL2RB, KLRB1, KLRC2, RHOF, RUNX3, and STAT4). A risk score model based on these genes stratified AML patients into high-risk and low-risk groups, with significant differences in survival prognosis between the two groups. RT-qPCR and Western blot analyses showed that these genes were significantly downregulated in AML patients. Flow cytometry results revealed significantly lower levels of NKT and CD8 + T cells in AML patients compared to controls.
This study identified key prognostic genes in AML and highlighted the critical role of NKT cells in AML pathogenesis. The study provides new insights and potential biomarkers for understanding AML biology, prognosis, and therapeutic targets.
急性髓系白血病（AML）是一种具有复杂免疫微环境特征的血液系统恶性肿瘤。本研究旨在鉴定AML中与免疫相关的预后生物标志物。
利用多个公共测序数据集分析AML中差异表达基因（DEG）。还进行了单样本基因集富集分析（ssGSEA）和加权基因共表达网络分析（WGCNA）。在单细胞水平评估免疫细胞浸润。将自然杀伤T（NKT）细胞标记基因与最相关的AML模块基因进行交集分析以鉴定关键基因。使用Cox Lasso回归模型筛选预后基因，并通过Cox随机森林和Kaplan-Meier生存分析评估其预后价值。通过逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法验证基因表达，并通过流式细胞术分析免疫细胞水平。
在AML与对照之间共获得1919个常见DEG。WGCNA显示棕色模块与AML的相关性最强。单细胞分析表明AML患者中NKT细胞浸润显著减少，与ssGSEA结果一致。在NKT细胞标记基因与棕色模块基因之间鉴定出40个交集基因。Cox Lasso回归鉴定出10个预后基因（FGFBP2、颗粒酶B、颗粒酶H、IKZF3、白细胞介素2受体β链、杀伤细胞凝集素样受体亚家族B成员1、杀伤细胞凝集素样受体亚家族C成员2、RHOF、RUNX3和信号转导和转录激活因子4）。基于这些基因的风险评分模型将AML患者分为高风险和低风险组，两组生存预后存在显著差异。RT-qPCR和蛋白质免疫印迹分析表明这些基因在AML患者中显著下调。流式细胞术结果显示，与对照相比，AML患者中NKT和CD8 + T细胞水平显著降低。
本研究鉴定了AML中的关键预后基因，并突出了NKT细胞在AML发病机制中的关键作用。该研究为理解AML生物学、预后和治疗靶点提供了新的见解和潜在生物标志物。
