生物信息学鉴定青少年特发性脊柱侧凸关键生物标志物OA
Identification of key biomarkers in adolescent idiopathic scoliosis by bioinformatics analysis
目的 对青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)患者间质干细胞的基因芯片数据进行生物信息学分析,探究AIS致病机制和治疗靶点.方法 从基因表达综合数据库(gene expression omnibus,GEO)下载基因芯片GSE110359,获取AIS患者与非AIS患者间质干细胞中的基因表达谱.利用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)识别AIS关键模块,并对其进行基因本体(gene ontology,GO)功能分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析;同时,对其 28 种不同类型免疫细胞进行免疫细胞浸润分析和蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,并筛选出核心基因.结果 确定 8 个基因共表达模块,GO富集在对氧减少的反应水平、低氧反应、对氧水平的反应、核糖核蛋白复杂组装、胶原蛋白-包含细胞外基质、剪接体snRNP复合物、snRNA结合、细胞外基质结构组成,KEGG信号通路富集在低氧诱导因子-1 信号通路、剪接体、细胞铁死亡、脂肪酸降解等通路.此外,免疫浸润结果发现,AIS 组单核细胞较非AIS组明显减少(P<0.05);而AIS组的活化树突状细胞浸润程度更高(P<0.05),通过PPI分析,筛选出血管生成素样4(angiopoietin-like 4,ANGPTL4)、CXC基序趋化因子配体 8(C-X-C motif chemokine ligand 8,CXCL8)、溶质载体家族 2 成员 1(solute carrier family 2 member 1,SLC2A1)、己糖激酶 2(hexokinase 2,HK2)、转铁蛋白受体蛋白(transferrin receptor protein,TFRC)在内的 5 个核心基因.结论 ANGPTL4、CXCL8、SLC2A1、HK2、TFRC是AIS患者的潜在生物标志物与治疗靶点,而单核细胞和活化树突状细胞可能是AIS患者的重要免疫治疗靶点.
Objective This study aims to investigate the pathogenesis and identify potential therapeutic targets for adolescent idiopathic scoliosis(AIS)through the utilization of bioinformatics analysis on gene chip data obtained from mesenchymal stem cells.Methods The gene chip GSE110359 was acquired from the gene expression omnibus(GEO)database to procure the gene expression profiles of mesenchymal stem cells derived from AIS and non AIS patients.Weighted gene co-expression network analysis(WGCNA)method was employed to identify the principal modules associated with adolescent idiopathic scoliosis.Furthermore,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted.Additionally,immune cell infiltration analysis and protein-protein interaction(PPI)analysis were performed on 28 distinct immune cell types,leading to the identification of core genes.Results A total of eight gene co-expression modules were successfully identified.GO analysis revealed significant enrichment in various biological processes,including response to decreased oxygen levels,response to oxygen levels,ribonucleoprotein complex subunit organization,collagen-containing extracellular matrix,spliceosome snRNP complex,snRNA binding,and extracellular matrix structural components.KEGG analysis demonstrated enrichment in several pathways,such as hypoxia-inducible factor-1 signaling pathway,spliceosome,ferroptosis,fatty acid degradation,and other pathways.Furthermore,the findings pertaining to immune infiltration revealed a noteworthy decrease in the quantity of monocytes within the AIS group compared to the non AIS group(P<0.05).There was a heightened level of infiltration by activated dendritic cells in the AIS group(P<0.05).PPI analysis was conducted,resulting in the identification of angiopoietin-like 4(ANGPTL4),C-X-C motif chemokine ligand 8(CXCL8),solute carrier family 2 member 1(SLC2A1),hexokinase 2(HK2),and transferrin receptor protein(TFRC).Conclusion ANGPTL4,CXCL8,SLC2A1,HK2 and TFRC have been identified as potential biomarkers and therapeutic targets of AIS patients.Monocytes and activated dendritic cells have emerged as significant targets for immunotherapy in the context of AIS.
徐海鹏;姜雅亨;文亚;刘晨;王恺骐;杜红根
浙江中医药大学附属第一医院(浙江省中医院)推拿科,浙江杭州 310006
临床医学
青少年特发性脊柱侧凸加权基因共表达网络分析生物信息学
Adolescent idiopathic scoliosisWeighted gene co-expression network analysisBioinformatics
《中国现代医生》 2024 (018)
1-7,12 / 8
浙江省科技计划项目(2022C03101)
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