KLF1在急性髓系白血病中的表达及临床意义研究

doi:10.19586/j.2095-2341.2025.0074

生物技术进展 ›› 2025, Vol. 15 ›› Issue (5): 904-912.DOI: 10.19586/j.2095-2341.2025.0074

KLF1在急性髓系白血病中的表达及临床意义研究

袁佳佳(), 邵欢()

无锡市第二人民医院（江南大学附属中心医院）药学部，江苏无锡 214002

收稿日期:2025-07-01 接受日期:2025-08-18 出版日期:2025-09-25 发布日期:2025-11-11
通讯作者: 邵欢
作者简介:袁佳佳 E-mail: yuan_jiajia2022@163.com；
基金资助:
2025无锡市科协软课题(KX-25-C066)

Study on the Expression and Clinical Significance of KLF1 in Acute Myeloid Leukemia

Jiajia YUAN(), Huan SHAO()

Department of Pharmacy，Wuxi No. 2 People's Hospital（Jiangnan University Medical Center），Jiangsu Wuxi 214002，China

Received:2025-07-01 Accepted:2025-08-18 Online:2025-09-25 Published:2025-11-11
Contact: Huan SHAO

摘要/Abstract

摘要：

急性髓系白血病（acute myeloid leukemia，AML）是一类以髓系细胞异常增殖及分化阻滞为特征的恶性造血性疾病。利用数据库中患者的转录组信息和临床信息分析Krueppel样因子1(Krueppel like factor 1，KLF1)在AML患者中的表达情况，使用R语言中的“Survival”和“Survminer”包进行生存分析。将患者分为KLF1高表达和低表达2组，进行差异基因功能富集分析。采用STRING在线数据库构建差异基因的蛋白互作网络图，利用Cytoscape软件筛选出核心基因，通过“pRRophetic”包预测潜在药物IC₅₀值，并对靶向KLF1低表达药物进行筛选。结果发现，KLF1在AML患者中表达显著下调，且KLF1低表达与不良预后相关。在KLF1低表达组和高表达组之间共筛选出1 017个差异基因，差异基因功能分析表明KLF1低表达组富集在免疫应答相关通路。筛选出CD4是KLF1低表达导致AML预后不良的关键基因。药物敏感性预测表明KLF1低表达细胞对细胞周期、激酶相关抑制剂具有敏感性。研究结果提示KLF1低表达可预测AML不良预后，可进一步为AML的诊断和治疗提供新的方案。

关键词: 急性髓系白血病, KLF1, 差异基因表达, 蛋白互作网络

Abstract:

Acute myeloid leukemia （AML） is a kind of malignant hematopoietic disorders characterized by abnormal proliferation and differentiation arrest of myeloid cells. The transcriptome information and clinical information of patients in the database were used to analyze the expression of Krueppel-like factor 1（KLF1） in AML patients. "Survival" and "Survminer" packages were used for survival analysis. The patients were divided into two groups by high and low expression of KLF1， and differential gene analysis was performed to analyze the functional enrichment. The protein-protein interaction networks （PPI） diagram of differentially expressed genes was constructed by STRING online database， and the core genes were screened by Cytoscape software. The IC₅₀ value of potential drugs was predicted by pRRophetic， and medicines targeting low expression of KLF1 were screened. It was found that the expression of KLF1 was significantly down-regulated in AML patients， and the low expression of KLF1 was associated with poor prognosis. A total of 1 017 differential expression genes （DEGs） were screened between the low and high expression groups of KLF1， and the enrichment analysis of DEGs functional pathways showed that the immune response-related pathways of the KLF1 low expression group were screened. CD4 is the hub gene with low expression of KLF1 leading to poor prognosis in AML. Drug susceptibility predictions suggested a number of inhibitors associated with cell cycle and kinases. The results suggested that low expression of KLF1 can predict the poor prognosis of AML， and further provide new solutions for the diagnosis and treatment of AML.

Key words: acute myeloid leukemia, Krueppel-like factor 1, differential expression genes, orotein-protein interaction networks

中图分类号:

Q814.4

袁佳佳, 邵欢. KLF1在急性髓系白血病中的表达及临床意义研究[J]. 生物技术进展, 2025, 15(5): 904-912.

Jiajia YUAN, Huan SHAO. Study on the Expression and Clinical Significance of KLF1 in Acute Myeloid Leukemia[J]. Current Biotechnology, 2025, 15(5): 904-912.

图/表 5

图1 AML患者中KLF1的表达水平与不良临床特征的关系A：根据GTEx、TCGA数据库中样本信息比较KLF1在各癌种中的表达情况；B：根据GTEx、TCGA数据库中样本信息比较AML患者与正常人的KLF1表达情况；C：GSE13159数据集中正常人与AML患者KLF1表达情况比较；D：生存状态；E：IDH1R140突变；两组数据之间显著性采用Wilcoxon 检验,多组数据之间显著性采用Kruskal-Wallis检验。ns表示组间无明显差异, *、**、***、****分别表示差异在P<0.05、P<0.01、P<0.001、P<0.000 1水平有统计学意义。

Fig. 1 The relationship of expression of KLF1 in AML and adverse clinical features

图2 KLF1低表达可预测AML不良预后A：TCGA-LAML数据集；B：GSE12417数据集；C：森林图显示影响AML患者生存的单因素生存分析结果；D：森林图显示影响AML患者生存的多因素生存分析结果

Fig. 2 Low expression of KLF1 predicts worse prognosis in AML

图3 基于KLF1表达的功能富集分析A：差异基因火山图；B：差异基因的KEGG分析结果；C~E：GO分析结果；F~H：GSEA分析结果

Fig. 3 Functional enrichment analysis based on KLF1 expression

图4 CD4是与KLF1表达相关的核心基因A：TCGA-LAML数据集中与KLF1共表达的基因分析；B：与KLF1共表达呈正相关的排名前10的基因；C：与KLF1共表达呈负相关的排名前10的基因；D：EPC模块分析；E：Degree模块分析；F：MNC模块分析；G：3种模块分析交集； H：CD4在AML患者与正常人中的表达情况比较；I：根据CD4表达高低分析AML患者生存时间

Fig. 4 Identification of CD4 as the hub gene connected with KLF1 expression

图5 KLF1低表达细胞的化疗药物敏感性分析A~L：在KLF1低表达组中，RO-3306、顺铂、放线菌素、表柔比星、吉西他滨、吉非替尼、Pevonedistat、司美替尼、IAP_5620_1428、优立替尼、SCH772984、达珀利奈的IC50值均较低，说明该组患者对药物更敏感。**、***、**** 分别表示差异在P<0.01、P<0.001、P<0.000 1水平上具有统计学意义。

Fig. 5 Drug sensitivity analysis of AML cells with low KLF1 expression

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KLF1在急性髓系白血病中的表达及临床意义研究

Study on the Expression and Clinical Significance of KLF1 in Acute Myeloid Leukemia

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