肺转移瘤巨噬细胞亚群差异表达基因的生物信息学分析  

Bioinformatics analysis of differentially expressed genes in macrophage subsets of lung metastases

作　　者：梁尹攀 邵俊杰 张蕾 管衍娇 伊淑莹 LIANG YinPan;SHAO Junjie;ZHANG Lei;GUAN Yanjiao;YI Shuying(Clinical and Basic Medical College&Institute of Basic Medical Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250117,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)临床与基础医学院(基础医学研究所),山东济南250117

出　　处：《山东第一医科大学（山东省医学科学院）学报》2024年第12期719-725,共7页Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences

基　　金：国家自然科学基金(81971512)。

摘　　要：目的 探究巨噬细胞亚群在肺转移瘤中的作用及机制,寻找小鼠肺转移瘤中肺泡巨噬细胞(alveolar macrophages,AMs)与肺间质巨噬细胞(interstitial macrophages,IMs)表达的差异基因及信号通路。方法 从基因表达数据库(gene expression omnibus,GEO)中获得小鼠黑色素瘤肺转移单细胞转录组测序(single-cell RNA sequencing,scRNAseq)数据GSM5235892。通过生物信息学分析技术,筛选AMs与IMs潜在的差异表达基因(differential expression analysis,DEGs)并进行基因本体论(gene ontology,GO)富集分析、京都基因与基因百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路分析、蛋白质相互作用(protein-protein interaction,PPI)分析及筛选前10位枢纽基因。最后通过qPCR检测核心基因在小鼠黑色素瘤肺转移模型AMs与IMs中的表达水平。结果 共鉴定出1975个AMs与IMs的DEGs,其中1511个上调基因,464个下调基因。GO富集分析和KEGG通路分析结果发现,DEGs主要涉及免疫反应、肿瘤细胞免疫调控、神经元突触免疫突触、生长因子受体活性等;涉及的信号通路为MAPK、NF-κB、TNF-α等信号通路。PPI分析筛选前10位的枢纽基因与细胞氧化磷酸化有关,包括Ndufa8、Cox6b1、Uqcr11、Cox5a、Ndufs6、Ndufs5、Uqcr10、Uqcrq、Ndufb6、Ndufab1;通过qPCR检测发现,枢纽基因Uqcr11、Ndufa5在肺转移瘤AMs中表达高于IMs,与生物信息分析结果一致。结论 通过scRNAseq数据生物信息学分析筛选得到的黑色素瘤肺转移小鼠AMs和IMs表达的枢纽基因和信号通路,可为黑色素瘤肺转移发病机制的研究提供参考。Objective:This article is to explore the role and mechanism of macrophage subsets in lung metastases,and to explore the differential genes and signaling pathways expressed by alveolar macrophages and interstitial macrophages in mouse lung metastases.Methods:Single-cell RNA sequencing(seRNAseq)data GSM5235892 were obtained from the gene expression database of mouse melanoma lung metastasis.Bioinformatic analysis techniques were used to screen potential differential genes of and to conduct gene ontology enrichment analysis,Kyoto Encyclopedia of Genes and Genes pathway analysis,protein interaction analysis and screening to identify the top 10 genes with high scores.Finally,the expression levels of core genes in mouse melanoma lung metastasis model alveolar macrophages and interstitial macrophages were detected by qPCR.Results:A total of 1975 differentially expressed genes of alveolar macrophages and interstitial macrophages were identified,including 1511 up-regulated genes and 464 down-regulated genes.Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes pathway analysis showed that the genes were mainly involved in immune response,tumor cell immune regulation,neuronal synaptic immune synapse,growth factor receptor activity,etc.The signaling pathways involved were NF-κB,TNF-α,MAPK,etc.The top 10 hub genes in PPI analysis were related to cellular oxidative phosphorylation,including Ndufa8,Cox6b1,Uqcr11,Cox5a,Ndufs6,Ndufs5,Uqcr10,Uqcrq,Ndufb6,Ndufab1;Through qPCR detection,we found that the expressions of hub gene Uqcr11,Ndufa5 were higher in alveolar macrophages and interstitial macrophages,which was consistent with the results of bioinformatics analysis.Survival analysis showed that the expression of the key gene Cox5a was associated with the survival of patients with skin melanoma.Conclusion:Through scRNAseq data bioinformatics analysis method,the key genes and signaling pathways expressed by alveolar macrophages and interstitial macrophages in mice with melanoma lung metastasis were scree

关 键 词：肺转移瘤 巨噬细胞亚群 生物信息学 差异表达基因 

分 类 号：R734.2[医药卫生—肿瘤]