骨关节炎关节滑膜组织差异表达基因生物学功能及与免疫细胞浸润的关系分析  

Biological function analysis of differentially expressed genes in synovial tissues of osteoarthritis and their relationships with immune cell infiltration

作　　者：冯重阳 姬振伟 王志学 张智翔 王银歌 吴鹏 丁勇 FENG Chongyang;JI Zhenwei;WANG Zhixue;ZHANG Zhixiang;WANG Yinge;WU Peng;DING Yong(Department of Orthopaedics,Second Affiliated Hospital of Air Force Medical University,Xi'an 710038,China)

机构地区：[1]空军军医大学第二附属医院骨科,西安710038 [2]中国人民解放军联勤保障部队第922医院骨科

出　　处：《山东医药》2022年第15期17-21,共5页Shandong Medical Journal

基　　金：陕西省重点研发计划项目(2020SF-094)。

摘　　要：目的筛选骨关节炎(OA)关节滑膜组织差异表达基因并分析其生物学功能,探讨核心差异表达基因与免疫细胞浸润的相关性。方法从Gene Expression Omnibus数据库筛选符合条件的基因芯片GSE55235、GSE55457、GSE1919和GSE12021,筛选上述四个数据集共有的正常和OA关节滑膜组织差异表达基因,应用DA⁃VID对差异表达基因进行生物学功能分析。采用STRING在线分析平台构建差异表达基因蛋白质互作网络,筛选核心差异表达基因。采用CIBERSORT方法分析正常和OA关节滑膜组织免疫细胞浸润情况以及核心差异表达基因与免疫细胞浸润的相关性。结果相对于正常关节滑膜组织,OA关节滑膜组织差异表达基因共1418个,其中692个上调、726个下调。OA和正常关节滑膜组织差异表达基因本体功能主要有酰胺结合、DNA结合转录因子结合、糖胺聚糖结合等,参与的信号通路主要有人类T细胞白血病病毒感染、TNF信号通路、类风湿性关节炎等。RPL37A、MYC、CDC20是OA的关节滑膜组织核心差异表达基因。与正常滑膜组织相比,OA患者关节滑膜组织中记忆B细胞、浆细胞、辅助性T细胞和静息肥大细胞所占比例较多,而静息记忆性CD4^(+)T细胞、嗜酸性粒细胞和活化肥大细胞所占比例较少(P均<0.05);RPL37A、MYC、CDC20与免疫细胞浸润关系密切(P均<0.05)。结论OA关节滑膜组织差异表达基因共1418个,其中692个上调、726个下调,基因本体功能主要有酰胺结合、DNA结合转录因子结合等,参与人类T细胞白血病病毒感染、TNF信号通路等;OA的核心差异表达基因是RPL37A、MYC、CDC20,与免疫细胞浸润关系密切。Objective To screen the differentially expressed genes in the synovial tissues of osteoarthritis(OA)joints,to analyze their biological functions,and to explore the correlations between core differentially expressed genes and immune cell infiltration.Methods The eligible datasets GSE55235,GSE55457,GSE1919 and GSE12021 were screened from the Gene Expression Omnibus database,and the differentially expressed genes in normal and OA joint syno⁃vial tissues shared by the above four datasets were screened,and DAVID was used to analyze the biological functions of the differentially expressed genes.The STRING online analysis platform was used to construct a protein-protein interaction net⁃work of differentially expressed genes,and we screened the core differentially expressed genes.The CIBERSORT method was used to analyze the infiltration of immune cells in normal and OA joint synovial tissues and the correlation between core differentially expressed genes and immune cell infiltration.Results Compared with the normal synovial tissues,there were 1418 differentially expressed genes in OA joint synovial tissues,of which 692 were up-regulated and 726 were downregulated.Gene ontology functions of differentially expressed genes in OA and normal joint synovial tissue mainly included amide binding,DNA binding transcription factor binding,glycosaminoglycan binding,etc.The signal pathways in volved mainly included human T-cell leukemia virus infection,TNF signal pathway,and rheumatoid arthritis,etc.RPL37A,MYC,and CDC20 were core differentially expressed genes in the OA joint synovial tissues.Compared with the normal synovial tissues,the proportion of memory B cells,plasma cells,helper T cells and resting mast cells in the synovi⁃al tissues of OA patients was higher,while resting memory CD4+T cells,eosinophils and activated mastocytes accounted for less(all P<0.05);RPL37A,MYC,and CDC20 were closely related to immune cell infiltration(all P<0.05).Con⁃clusions There were 1418 differentially expressed genes in the synovial tissu

关 键 词：骨关节炎相关基因 基因功能 免疫细胞 细胞浸润 免疫功能 骨关节炎 

分 类 号：R684.3[医药卫生—骨科学]