Data Sheet 2_Identification of hub genes and immune-related pathways in acute myeloid leukemia: insights from bioinformatics and experimental validation.pdf

BackgroundThis study aims to identify the hub genes and immune-related pathways in acute myeloid leukemia (AML) to provide new theories for immunotherapy.
MethodsWe use bioinformatics methods to find and verify the hub gene. At the same time, we use the results of GSEA enrichment analysis to find immune-related mediators. Through Mendelian randomization(MR) analysis, on the one hand, we look for related immune cells, and on the other hand, we use it to determine the causal relationship among immune cells, immune mediators, and AML. Finally, in vitro experiments are conducted to further verify and improve the reliability and physiological functions of the hub gene and its immune-related pathways.
ResultsComplement Factor D(CFD) gene is identified as the highly expressed hub gene and is positively correlated with IL-2. IL-2 is also positively correlated with CD27 on CD24+CD27+B cells, JAK/STAT, and PI3K/Akt. The latter three are positively correlated with the occurrence and development of AML.
ConclusionWe conclude that CFD gene uses IL-2 as a mediator to promote the disease progression of AML by promoting the CD27 on CD24+CD27+B cells, JAK-STAT, and PI3K-Akt pathways.

**背景** 本研究旨在明确急性髓系白血病（acute myeloid leukemia, AML）中的核心基因（hub gene）与免疫相关通路，为免疫治疗提供全新理论依据。
**方法** 本研究采用生物信息学方法筛选并验证核心基因（hub gene）；同时借助基因集富集分析（Gene Set Enrichment Analysis, GSEA）的富集结果，挖掘免疫相关介质。通过孟德尔随机化（Mendelian randomization, MR）分析，一方面筛选关联免疫细胞，另一方面明确免疫细胞、免疫介质与急性髓系白血病之间的因果关联。最后开展体外实验，进一步验证并提升核心基因及其免疫相关通路的可靠性与生理功能相关性。
**结果** 本研究鉴定出补体因子D（Complement Factor D, CFD）为高表达核心基因，且其与白细胞介素2（Interleukin-2, IL-2）呈正相关；白细胞介素2（IL-2）亦与CD24+CD27+B细胞表面CD27、Janus激酶/信号转导与转录激活子（Janus kinase/Signal transducer and activator of transcription, JAK/STAT）通路及磷脂酰肌醇3-激酶/蛋白激酶B（Phosphatidylinositol 3-kinase/Protein kinase B, PI3K/Akt）通路呈正相关，而上述三者均与急性髓系白血病的发生发展呈正相关。
**结论** 本研究证实，补体因子D（CFD）基因以白细胞介素2（IL-2）为介导，通过调控CD24+CD27+B细胞表面CD27、JAK-STAT及PI3K-Akt信号通路，促进急性髓系白血病的疾病进展。