首页|骨关节炎滑膜组织中细胞焦亡基因的生物信息学分析与药物筛选

骨关节炎滑膜组织中细胞焦亡基因的生物信息学分析与药物筛选

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  • NETL
  • NSTL
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目的 应用生物信息学方法筛选骨关节炎(OA)滑膜组织中差异表达细胞焦亡基因及潜在治疗药物.方法 GEO55235数据集中获取细胞焦亡相关差异表达基因(PRDEGs),并对其进行富集分析、聚类分析和免疫浸润分析.使用蛋白-蛋白相互作用网络(PPI)识别关键基因,采用受试者特征曲线(ROC)分析关键基因诊断价值,利用Coremine Medical数据库筛选靶向关键基因的化合物和中药.最后,荧光实时定量聚合酶联反应(qRT-PCR)验证关键基因在正常和OA滑膜组织中的表达差异,并采用独立样本t检验比较其差异.结果 GEO55235数据集中共筛选获得13个差异表达细胞焦亡基因,其主要富集细胞程序性死亡、免疫调控、炎性反应等生物学过程以及肿瘤坏死因子(TNF)、核因子-κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)等信号通路.此外,13个PRDEGs的表达与免疫细胞浸润密切相关,两种OA滑膜组织亚型之间免疫细胞丰度存在明显差异.PPI和ROC曲线分析提示含PYD和CARD域蛋白(PYCARD)是OA滑膜组织中的关键焦亡基因,具有较好的诊断价值.Coremine Medical数据库中筛选到多种可作用于PYCARD基因的化合物和中药.qRT-PCR结果表明,PYCARD在OA组(2.690±1.355)的表达高于正常组(1.039±0.400,t=3.050,P＜0.05).结论 滑膜细胞焦亡与OA发生密切相关,其中PYCARD基因可能是一种诊断和治疗OA滑膜炎症的标志物和靶点.
Bioinformatics analysis and drug screening of pyroptosis related genes in the synovial tissues of oste-oarthritis
Objective To screen pyroptosis related differentially expressed genes(PRDEGs)and potential therapeutic drugs in synovium of osteoarthritis(OA)using bioinformatics.Methods PRDEGs were obtained from GEO55235 dataset,and enrichment analysis,cluster analysis and immune infiltration were further conducted.Hub genes were identified using protein-protein interaction(PPI),receiver operat-ing characteristic(ROC)curve was used to determine their diagnostic value,and Coremine Medical data-base was used to screen compounds and Chinese medicines targeting hub genes.Finally,quantitative real-time PCR(qRT-PCR)was adopted to verify the difference of hub genes between normal and OA synovium.Results A total of 13 PRDEGs were screened in GEO55235 dataset,which were mainly enriched in mul-tiple biological processes such programmed cell death,immune infiltration,inflammatory response,and signaling pathways such as tumor necrosis factor(TNF),nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK).In addition,the expression of 13 PRDEGs was closely related to immune infiltra-tion,and there were significant differences in the abundance of immune cells between two subtypes of OA synovium.The results of PPI and ROC analysis suggested that PYCARD functioned as a key gene which had good diagnostic value in OA synovium.Multiple compounds and Chinese medicines targeting PYCARD were screened in Coremine Medical database.qRT-PCR confirmed that the expression of PYCARD in OA group(2.690±1.355)was higher than that in normal group(1.039±0.400,t=3.050,P＜0.05).Conclusion The pyroptosis of synoviocytes is closely related to the development of OA,and PYCARD may be a biomarker and target for the diagnosis and treatment of OA synovitis.

OsteoarthritisSynovitisPyroptosisPyroptosis related differentially expressed genesImmune infiltrationDrug screening

孙红、陈坤浩、彭国璇、熊治林、邓进、杨华

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贵州医科大学附属医院骨科,贵阳 550004

贵州医科大学附属医院急诊外科,贵阳 550004

骨关节炎 滑膜炎 细胞焦亡 细胞焦亡相关差异表达基因 免疫浸润 药物筛选

贵州省科技厅基础研究计划贵州省科技厅基础研究计划贵州省卫生健康委科学技术基金贵州省卫生健康委科学技术基金贵州省研究生科研基金贵州医科大学附属医院国家自然科学基金青年基金培育计划

黔科合基础-ZK[2021]391黔科合基础-ZK[2023]一般344gzwjkj2020-1-120gzwkj2021-261YJSKYJJ[2021]157gyfynsfc-2021-12

2024

10.3760/cma.j.cn421213-20230710-00403

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子：0.759
ISSN：1001-9030
年,卷(期)：2024.41(4)
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