Shan Mingliang, Xu Li, Yang Wenzhe, Sui Lili, Sun Ping, Zhuo Xiumei, Liu Shiguo
Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China.
Post - Doctoral Innovation Practice Base, Gaomi Maternity and Child Health Hospital, Gaomi, China.
Front Immunol. 2025 May 8;16:1547289. doi: 10.3389/fimmu.2025.1547289. eCollection 2025.
Aplastic anemia (AA), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML) exhibit complex pathogenic mechanisms and interrelated characteristics. We aimed to identify the common hub genes, establishing a foundation for preventing disease progression.
We selected relevant datasets from the Gene Expression Omnibus(GEO) database for differential gene expression, gene set enrichment, and weighted gene co-expression network analyses to identify hub genes, and then validated them. Subsequent analyses included immune infiltration analysis, single-cell sequencing, and cell communication analysis. We performed Mendelian randomization to screen inflammatory factors and immune cells. We used RT-qPCR, Enzyme - Linked Immunosorbent Assay(ELISA), and cell proliferation assays to validate the identified hub genes, their relationship with cellular communication mediators and inflammatory factors, and their impact on cellular function.
POLG and MAP2K7 were identified as common hub genes, with low expression observed across AA, MDS, and AML. There were distinct immune differentials among these diseases, with an enhanced correlation between immune cells and hub genes as the disease progressed. Macrophage Migration Inhibitory Factor(MIF) emerged as a key mediator of cellular communication. We identified 20 regulatory pathways of immune cells and inflammatory factors across different disease stages. validation confirmed low expression of the hub genes, which were inversely correlated with MIF and inflammatory factors, though they showed no significant impact on cell proliferation or migration.
POLG and MAP2K7 demonstrate crucial roles in the progression from AA to MDS and, ultimately, to AML. These genes regulate more than 20 immune regulatory pathways through MIF-mediated communication, thereby influencing disease progression.
再生障碍性贫血（AA）、骨髓增生异常综合征（MDS）和急性髓系白血病（AML）表现出复杂的致病机制和相互关联的特征。我们旨在识别共同的枢纽基因，为预防疾病进展奠定基础。
我们从基因表达综合数据库（GEO）中选择相关数据集进行差异基因表达、基因集富集和加权基因共表达网络分析，以识别枢纽基因，然后对其进行验证。后续分析包括免疫浸润分析、单细胞测序和细胞通讯分析。我们进行孟德尔随机化以筛选炎症因子和免疫细胞。我们使用逆转录定量聚合酶链反应（RT-qPCR）、酶联免疫吸附测定（ELISA）和细胞增殖测定来验证所识别的枢纽基因、它们与细胞通讯介质和炎症因子的关系以及它们对细胞功能的影响。
POLG和MAP2K7被确定为共同的枢纽基因，在AA、MDS和AML中均观察到低表达。这些疾病之间存在明显的免疫差异，随着疾病进展，免疫细胞与枢纽基因之间的相关性增强。巨噬细胞迁移抑制因子（MIF）成为细胞通讯的关键介质。我们确定了不同疾病阶段免疫细胞和炎症因子的20条调控途径。验证证实枢纽基因表达较低，它们与MIF和炎症因子呈负相关，尽管它们对细胞增殖或迁移没有显著影响。
POLG和MAP2K7在从AA进展到MDS以及最终进展到AML的过程中发挥着关键作用。这些基因通过MIF介导的通讯调节超过20条免疫调节途径，从而影响疾病进展。
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