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急性髓系白血病中与能量代谢相关的枢纽基因的鉴定与功能探索

英文原题:Identification and functional exploration of hub genes related to energy metabolism in acute myeloid leukemia.

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Identification and functional exploration of hub genes related to energy metabolism in acute myeloid leukemia.

PubMed 2026/03/02(内容时间) Hematology Q3 · IF 2(JCR 2025)

研究概要

AML对化疗反应差。鉴定出6个与代谢、通路(核糖体、免疫、NOD)和药物靶点(如Lapatinib/CDH1)相关的枢纽基因。讨论了CDH1与NK细胞的相关性。这些枢纽基因为未来AML个体化治疗提供了有前景的靶点。

研究思路结论见上方概要

急性髓系白血病(AML)是一种侵袭性血液系统恶性肿瘤,预后较差。能量代谢异常是公认的癌症标志,但能量代谢相关基因(EMRGs)在AML中的作用仍不清楚。因此,本研究旨在鉴定AML中的此类枢纽基因,并探讨其预后意义、相关通路及治疗靶向潜力。

从公共数据库获取AML相关数据集和EMRGs。通过差异表达分析、相关性分析和PPI分析等鉴定枢纽基因。随后,进行集合富集分析。构建药物-基因网络,并进行免疫微环境分析。

本研究识别出6个枢纽基因(CDH1、AGRN、NDST3、GPC3、CD44和COL4A1),其表达水平与AML患者的总生存期显著相关。这些枢纽基因在各聚类间也表现出显著的表达差异;例如,CD44在聚类2中上调,而COL4A1和GPC3则下调。功能富集分析显示,它们与“核糖体”、“ECM-受体相互作用”等功能通路相关。因此,基于这些枢纽基因预测出拉帕替尼、庆大霉素等药物,并且我们发现CDH1与多种细胞(如NK细胞和T细胞)呈正相关,其中CDH1与NK细胞的正相关性最高。

展开英文摘要原文

OBJECTIVES: Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor prognosis. Abnormal energy metabolism is a well-recognized cancer hallmark, yet the role of energy metabolism-related genes (EMRGs) in AML remains unclear. Thus, this study aims to identify such hub genes in AML and explore their prognostic significance, related pathways, and therapeutic targeting potential. METHODS: AML-related datasets and EMRGs were obtained from public databases. The hub gene was identified through differential expression analysis, correlation analysis and PPI analysis, etc. Then, a set enrichment analysis was conducted. A drug-gene network was constructed, and immune microenvironment analysis was performed. RESULTS: In this study, six hub genes (CDH1, AGRN, NDST3, GPC3, CD44, and COL4A1) were identified, and their expression levels were significantly associated with the overall survival of AML patients. These hub genes also exhibited significant expression differences among clusters; for instance, CD44 was upregulated in cluster 2, while COL4A1 and GPC3 were downregulated. Functional enrichment analysis showed that they were associated with 'ribosome', ECM-receptor interaction', and other functional pathways. Consequently, lapatinib, gentamicin, etc., were predicted based on the hub genes, and we found that CDH1 was positively correlated with multiple cells, such as NK cells and T cells, and there was the highest positive correlation between CDH1 and NK cells. DISCUSSION: AML shows a poor response to chemotherapy. Six hub genes linked to metabolism, pathways (ribosome, immune, NOD), and drug targets (e.g. Lapatinib/CDH1) were identified. Correlation of CDH1 with NK cells is discussed. CONCLUSION: These hub genes offer promising targets for future individualized AML therapy.

论文信息

作者
Chen Y、Ji Y、Qin W、Yan X
单位
Department of Hematology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, People's Republic of China.China
期刊
Hematology (Amsterdam, Netherlands)2026 Dec
原文标识
PubMed 41769961 · DOI 10.1080/16078454.2026.2637350