摘要
目的 利用生物信息学方法分析神经母细胞瘤骨髓转移差异表达的基因,探讨免疫细胞浸润情况,筛选参与神经母细胞瘤骨髓转移的关键基因.方法 在GEO数据库下载神经母细胞瘤骨髓转移相关数据集GSE112447,筛选差异表达基因(DEGs),进行GO/KEGG富集分析、蛋白互作网络构建、免疫浸润分析,利用Cytoscape软件筛选关键基因.结果 筛选得到397个DEGs,其中261个上调基因,136个下调基因.功能富集分析显示DEGs参与信号转导、炎症反应、细胞增殖等多种生物学过程.KEGG结果表明:DEGs与PI3K-Akt信号通路、破骨细胞分化、趋化因子信号通路等有关.22种免疫细胞中,相对于骨髓转移组,无骨髓转移组有更多的浆细胞、活化的CD4+T细胞、滤泡辅助T细胞、活化的NK细胞、M0及M2巨噬细胞浸润.PPI网络构建筛选得到9个关键基因(TNF、IL-1β、ITGAM、TLR2、FCGR3A、S100A12、FGR、LILRB2、HCK).ROC 曲线提示 S100A12及IL-1β高表达发生骨髓转移风险相对更高.结论 本研究筛选得到的关键基因及免疫细胞浸润水平的变化可能在神经母细胞瘤骨髓转移中起到重要作用.
Abstract
Objective To elucidate differentially expressed genes(DEGs)in neuroblastoma bone marrow metastasis through bioinformatics methodologies,investigate immune cell infiltration,and identify key genes implicated in neuroblastoma bone marrow metastasis.Methods The GSE112447 dataset,pertinent to neuroblastoma bone marrow metastasis,was procured from the GEO database.Subsequently,DEGs were identified through meticulous screening.Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(GO/KEGG)enrichment analysis,protein interaction network construction,and immune infiltration analysis were systematically performed.Key genes were discerned utilizing Cytoscape software.Results A total of 397 DEGs emerged from the screening process,encompassing 261 up-regulated genes and 136 down-regulated genes.Functional enrichment analysis revealed the involvement of DEGs in signal transduction,inflammatory response,cell proliferation,and various other biological processes.The KEGG results indicated DEGs associated with pathways such as the PI3K-Akt signaling pathway,osteoclast differentiation,and the chemokine signaling pathway.Among the 22 immune cell types analyzed,the non-bone marrow metastasis group exhibited a higher presence of plasma cells,T cells CD4 memory activated,T cells follicular helper,NK cells activated,M0,and M2 macrophages compared to the bone marrow metastasis group.Nine key genes(TNF,IL-1β,ITGAM,TLR2,FCGR3A,S100A12,FGR,LILRB2,HCK)were successfully identified through the construction of a protein-protein interaction(PPI)network.The Receiver Operating Characteristic curve(ROC)suggested that elevated expression of S100A12 and IL-1β was associated with an increased risk of bone marrow metastasis.Conclusions The key genes identified in this study,coupled with alterations in immune cell infiltration levels,may potentially exert a pivotal role in the context of neuroblastoma bone marrow metastasis.
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