摘要
背景:铁死亡及细胞焦亡可能在绝经后骨质疏松症的发生发展过程中起到作用,可能存在诊断绝经后骨质疏松症的相关生物标志物。目的:利用生物信息学手段寻找绝经后骨质疏松症过程中铁死亡及细胞焦亡相关的关键基因,以进一步阐明其生物学机制。方法:使用美国国家基因表达综合数据库(GEO数据库)下载绝经后骨质疏松症的数据集GSE56815和GSE7429,对两数据集进行预处理,借助R软件limma包进行数据差异表达分析,通过DIVID、KOBAS数据库进行富集分析,借助STRING、Cytoscape绘制蛋白互作网络,通过CytoHubba选取Hub基因,通过铁死亡基因数据库及细胞焦亡数据库筛选关键基因。利用CIBERSORT包测定绝经后骨质疏松症样本的免疫浸润情况,进行关键基因与免疫细胞的相关性分析。结果与结论:①于实验样本中共计筛选出30个绝经后骨质疏松症的差异基因,其中9个基因表达上调,21个基因表达下调;②GO、KEGG通路富集显示差异主要集中在丝氨酸型内肽酶活性、先天免疫反应、特殊颗粒管腔、肾素分泌等;③PPI网络显示差异基因的相关性,CytoHubba选出Degree值前10的Hub基因;④Hub基因与FerrDb铁死亡数据库及细胞焦亡数据集取交集得到关键基因ELANE、LCN2;⑤受试者工作特征曲线及箱图表明,ELANE、LCN2在绝经后骨质疏松症血清样本中的表达较正常样本明显降低,具有良好的诊断价值;⑥免疫浸润分析显示,ELANE可能与记忆性静息CD4 T细胞、M0巨噬细胞、M2巨噬细胞有关,LCN2可能与M0巨噬细胞有关。
BACKGROUND:Ferroptosis and pyroptosis may play a role in the development of postmenopausal osteoporosis.There may be relevant biomarkers for the diagnosis of postmenopausal osteoporosis.OBJECTIVE:To search for the key genes related to ferroptosis and pyroptosis in postmenopausal osteoporosis using bioinformatics so as to further elucidate their biological mechanisms.METHODS:The data sets GSE56815 and GSE7429 of postmenopausal osteoporosis were downloaded from the GEO database,the national comprehensive gene expression database of the United States,and the two data sets were preprocessed.The differential expression analysis of the data was carried out by the limma package of R software,and the enrichment analysis was performed by DIVID and KOBAS.The protein-protein interaction network was mapped by STRING and Cytoscape,the Hub gene was selected by CytoHubba,and the key genes were screened by the ferroptosis database and pyroptosis database.The CIBERSORT package was used to determine the immune infiltration of postmenopausal osteoporosis samples and to analyze the correlation between key genes and immune cells RESULTS AND CONCLUSION:A total of 30 differential genes of postmenopausal osteoporosis were screened in the experimental samples,of which 9 genes were up-regulated and 21 genes were down-regulated.The enrichment of GO and KEGG pathways showed that the differences were mainly in“serine-type endopeptidase activity,”“innate immune response,”“special particle lumen,”and“renin secretion.”The protein-protein interaction network showed the correlation of differential genes and the top 10 Hub genes with“Degree”value were selected using CytoHubba.Hub gene was intersected with the FerrDb database and cell pyroptosis dataset to obtain key genes ELANE and LCN2.Receiver operating characteristic curve and box diagram showed that the expression of ELANE and LCN2 in serum samples of postmenopausal osteoporosis was significantly lower than that in normal samples,indicating a good diagnostic value.Immune infiltration analysis showed that ELANE may be related to memory resting CD4+T cells,M0 and M2 macrophages.LCN2 may be related to M0 macrophages.
作者
李树栋
梁学振
骆帝
李嘉程
阎博昭
李刚
Li Shudong;Liang Xuezhen;Luo Di;Li Jiacheng;Yan Bozhao;Li Gang(First Clinical Medical School,Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,Shandong Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2024年第28期4511-4515,共5页
Chinese Journal of Tissue Engineering Research
基金
山东省重点研发计划项目(重大科技创新工程)(2021CXG0105010),项目负责人:李刚
山东省自然科学基金资助项目(ZR2020KH012),项目负责人:李刚。
