绝经后女性骨质疏松相关基因的生物信息学分析

Bioinformatics analysis of osteoporosis-related genes in postmenopausal women

目的基于生物信息学方法筛选并分析绝经后女性外周血单核细胞(PBMs)中与骨质疏松相关的差异表达基因。方法利用NCBI中的GEO基因芯片公共数据库进行数据分析,选择芯片数据(GSE56815)作为分析对象,采用R软件(3.6.1版)中的Limma程序包筛选差异表达基因,并应用R软件中的ClusterProfiler程序包对筛选出的表达上调的差异表达基因进行GO和KEGG富集分析,选用String数据库构建蛋白质-蛋白质相互作用(PPI)网络图。结果通过对GSE56815进行分析,共筛选出40个差异表达基因,其中上调基因34个和下调基因6个。34个上调差异表达基因GO分析发现,主要富集于中性粒细胞脱颗粒、免疫反应的中性粒细胞激活、对细菌来源的分子反应、对脂多糖的反应和细胞对生物刺激的反应;KEGG富集分析结果显示,上调差异表达基因主要富集到NOD样受体信号通路、金黄色葡萄球菌感染、成骨细胞的分化、糖类降解和精氨酸的生物合成等信号通路。采用String数据库构建的上调差异表达基因的PPI网络分析显示,CEACAM8、LTF、CRISP3、CAMP、LCN2、DEFA4、MMP8、ARG1、HP、BPI、CEACAM6、TCN1和ELANE蛋白存在着互作关系;上述关键差异表达基因GO富集分析发现,主要富集在中性粒细胞脱颗粒、抗菌肽、对脂多糖的反应、细胞外基质组织。结论CEACAM8、LTF、CAMP、LCN2、MMP8和ARG1与骨代谢的联系密切,可能是提示绝经后女性骨量变化的生物标记物。

Objective:To understand the molecular mechanisms underlying the development and progression of osteoporosis in postmenopausal women by screening for differentially expressed genes associated with reduced bone mass in peripheral blood monocytes(PBMs).Methods:The GEO gene chip public database in NCBI was used for data analysis,and the microarray data(GSE56815)was selected for analysis object.The Limma package in R software(version 3.6.1)was used to screen the differentially expressed genes,and the ClusterProfiler package in R software was applied to perform GO and KEGG enrichment analysis on the screened differentially expressed genes with up-regulated expression,and the String database was selected to construct protein-protein interaction(PPI)network maps.Results:By analyzing GSE56815,a total of 40 differentially expressed genes were screened,including 34 up-regulated genes and 6 down-regulated genes.GO analysis of 34 upregulated differentially expressed genes revealed that they were mainly enriched in neutrophil degranulation,neutrophil activation in response to immune response,response to molecules of bacterial origin,response to lipopolysaccharide and cellular response to biological stimuli.KEGG enrichment analysis found that the upregulated differentially expressed genes were mainly involved in signaling pathways such as NOD-like receptor signaling pathway,staphylococcus aureus infection,osteoblast differentiation,glycan degradation and arginine biosynthesis.PPI network analysis of upregulated differentially expressed genes constructed by using String database showed that there were interactions among CEACAM8,LTF,CRISP3 CAMP,LCN2,DEFA4,MMP8,ARG1,HP,BPI,CEACAM6,TCN1,and ELANE.GO enrichment analysis of the above key differentially expressed genes revealed that they were mainly enriched in neutrophil degranulation,antimicrobial peptides,response to lipopolysaccharide,and extracellular matrix organization.Conclusions:CEACAM8,LTF,CAMP,LCN2,MMP8 and ARG1 were closely linked to bone metabolism,and might be biomarkers suggesting changes in bone mass in postmenopausal women.