绝经后骨质疏松女性骨折相关基因筛选  

Screening of fracture related genes in postmenopausal women with osteoporosis

作　　者：林建立 陈耀琦 林移婷 胡张洁 蔡敏 Lin Jianli;Chen Yaoqi;Lin Yiting;Hu Zhangjie;Cai Min(Department of Endocrinology,Fuzhou University Affiliated Provincial Hospital,Fujian,Fuzhou 350001,China;Department of Nuclear Medicine,Fuzhou University Affiliated Provincial Hospital,Fujian,Fuzhou 350001,China;Cadre Speciality ClinicⅡ,Fuzhou University Affiliated Provincial Hospital,Fujian,Fuzhou 350001,China)

机构地区：[1]福州大学附属省立医院内分泌科,福建福州350001 [2]福州大学附属省立医院核医学科,福建福州350001 [3]福州大学附属省立医院干部特诊二科,福建福州350001

出　　处：《创伤与急诊电子杂志》2024年第4期268-277,共10页Journal of Trauma and Emergency(Electronic Version)

基　　金：福建省立医院“火石计划”基金项目(2019HSJJ20);福建省卫生健康委员会医学创新项目(2018-CXB-1);福建省卫生健康中青年骨干人才培养项目(2020GGA009);福建省自然科学基金(2023J011208)。

摘　　要：目的利用基因表达数据库(gene expression omnibus,GEO)及Affymetrix人类基因组U133A阵列探索绝经后骨质疏松症女性骨折创伤相关基因和调节基因的相关药物。方法选择GEO中GSE56815数据集,通过对应探针U133A对该数据集进行基因名注释,并从中提取绝经后骨质疏松的骨折女性40例和正常对照组40例作为后续研究对象。使用R软件中limma包进行分析,以筛选绝经后骨质疏松(postmenopausal osteoporosis,PMOP)女性患者相关差异基因(differential gene,DEG)。随后,利用行基因本体(gene ontology,GO)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DEG可能参与的功能与通路,利用蛋白质互作(protein-protein interaction,PPI)网络及Cytosacape软件鉴定DEG间相互关联并筛选枢纽基因(Highly connected gene,用“hub基因”表示),利用在线数据库DiseaseMeth进行hub基因的甲基化分析,构建小分子核糖核酸(MicroRNA,miRNA)-hub基因、转录因子(transcriptionfactors,TF)-hub基因共表达网络进一步探讨hub基因潜在骨折创伤的作用机制。结果共鉴定出219个DEG,富集分析显示DEG显著参与细胞转录、凋亡及免疫途径。外周血单核细胞在PPI网络中确定了7个hub基因,其中CCAAT增强子结合蛋白α(CCAAT enhancer-bindingproteinα,CEBPA)和血红素氧合酶1(hemeoxygenase1,HMOX1)上调PMOP骨折创伤相关基因的甲基化。药物-基因相互作用网络表明,共4种药物或分子化合物(白藜芦醇、环磷酰胺、阿司匹林、苏拉明)可调节HMOX1的表达。结论PMOP骨折创伤患者外周血单核细胞存在表达差异,其中包括HMOX1在内的7个下调基因在PMOP骨折创伤中发挥重要作用。这些生物信号可能在病理性骨折中共同发挥作用,从而导致PMOP骨折的发生发展。Objective To analyze transcriptome expression related to fracture trauma in postmenopausal osteoporotic women using the Gene Expression Omnibus(GEO)database and Affymetrix Human Genome U133A Array.Method The GSE56815 dataset from GEO was selected,and gene names were annotated through corresponding probes U133A.Forty cases of postmenopausal osteoporosis with fracture trauma and 40 normal control cases were extracted from the dataset for subsequent research.The R software's limma package was used for analysis to screen for DEGs related to postmenopausal osteoporosis(PMOP).Subsequently,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to explore the potential functions and pathways in which DEGs may be involved.Protein-protein interaction networks(PPIs)and Cytoscape software's Cytohubba plugin with five algorithms(Degree,MNC,DMNC,Closeness,Radiality)were utilized to identify DEG interrelations and screen for hub genes.Online database DiseaseMeth was used for methylation analysis of hub genes.A microRNA(miRNA)-hub gene,transcription factors(TF)-hub gene co-expression network was constructed to further explore the potential mechanisms of hub genes in fracture trauma.Result A total of 219 DEGs were identified,and enrichment analysis showed that DEGs were significantly involved in cellular transcription,apoptosis,and immune pathways.Seven hub genes were identified in the PPI network,two of which were hypermethylated in PMOP fracture trauma-related complications such as atherosclerosis.Conclusion There are expression differences in peripheral blood mononuclear cells of patients with PMOP fracture trauma,including seven downregulated genes,among which heme oxygenase 1(HMOX1)plays an important role in PMOP fracture trauma.They are mostly involved in the development of monocyte/macrophage lineage,osteoclast differentiation,and immune response to inflammation,which may collectively act in pathological fractures,leading to the occurrence and development of PMOP fracture traum

关 键 词：绝经后骨质疏松症 病理性骨折创伤 破骨细胞 生物信息学 枢纽基因 

分 类 号：R73[医药卫生—肿瘤]