摘要
目的利用生物信息学分析方法筛选多发性骨髓瘤(MM)患者骨髓间充质干细胞(BMMSCs)衰老相关差异表达基因(DEGs)及相关信号通路。方法从GEO公共数据库中下载MM患者与健康人BMMSCs基因表达矩阵GSE113736,再下载长寿群体(平均年龄93.4岁)与衰老群体(平均年龄61.9岁)的基因表达矩阵GSE16717;应用R软件筛选DEGs,获得MM患者BMMSCs中衰老相关的DEGs;运用STRING在线数据库及Cytoscape软件构建基因网络,筛选出显著模块及关键基因,对DEGs进行KEGG通路分析获取功能基因。然后,对功能基因与关键基因取交集获得hub基因。最后,采用GSE80608数据集验证hub基因筛选的准确性。结果通过分析获得372例MM患者BMMSCs中与衰老相关的DEGs。通路富集分析显示,DEGs在细胞凋亡、白介素介导的信号通路、蛋白质翻译后磷酸化和FOXO介导的信号通路等方面富集。通过进一步筛选,鉴定出MM患者BMMSCs中与衰老相关的4个hub基因,ANXA1、CKAP4、BTG1及ACTB。这4个hub基因在验证数据集GSE80608中亦有差异表达。结论MM患者BMMSCs的衰老现象可能与ANXA1、ACTB、CKAP4和BTG1的异常表达有关,通过影响细胞凋亡、白介素介导的信号通路、蛋白质翻译后的磷酸化及FOXO介导的转录,促进/加速MM患者BMMSCs衰老。
ObjectiveTo identify the differentially expressed genes (DEGs) and pathways involved in the senescence of bone marrow mesenchymal stem cells (BMMSCs) in patients with multiple myeloma (MM) based on bioinformatics analysis.MethodsThe BMMSCs-related gene expression matrix GSE113736 dataset of MM patients and healthy individuals and the ageing-related matrix GSE16717 dataset from healthy people, which included the longevity group with an average age of 93.4 years and the aging group with an average age of 61.9 years, were downloaded from the GEO database. Then the R software was applied to screen the DEGs, which are senescence-related in BMMSCs of MM. The STRING online database and Cytoscape software were used to construct the gene network from which the most significant modules and essencial genes were screened. The DEGs were analyzed on KEGG pathway to obtain the functional genes. Finally, hub genes were obtained by intersecting the two sets of functional genes and the key genes, and the accuracy of hub gene screening was verified by the GSE80608 data set.ResultsThere 372 senescence-related DEGs were screened out from BMMSCs of MM patients. The protein interaction network of DEGs was constructed by STRING and Cytoscape, and the important node genes in the network were screened out. DEGs were significantly enriched in the apoptotic signal pathway, signaling by interleukins, post-translational protein phosphorylation and FOXO-mediated transcription. Through further screening, four hub genes were identified as ANXA1, CKAP4, BTG1 and ACTB. These four hub genes were expressed significantly and differentially in the validation dataset GSE80608.ConclusionThe senescence of BMMSCs in MM patients may be related to the abnormal expression of ANXA1, ACTB, CKAP4 and BTG1;these genes accelerate and promote senescence by regulating apoptosis, interleukin-mediated signaling pathway, phosphorylation after protein translation, and FOXO-mediated transcription.
作者
周艳群
陈鹏
刘增慧
毛晶晶
黎耀和
Yanqun Zhou;Peng Chen;Zenghui Liu;Jingjing Mao;Yaohe Li(The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510000,China;Department of Hematology,The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000,China;Department of Infection,Shiqian County People's Hospital,Guizhou 555100,China)
出处
《中华细胞与干细胞杂志（电子版）》
2022年第5期274-281,共8页
Chinese Journal of Cell and Stem Cell（Electronic Edition）
基金
国家自然科学基金(81903973)
广东省中医药管理局中医药科研项目(20202050)。
关键词
骨髓间充质干细胞
衰老
多发性骨髓瘤
生物信息学
Bone marrow mesenchymal stem cells
Senescence
Multiple myeloma
Bioinformatics
