铜死亡调节因子在骨关节炎诊断及亚分型中的作用  

Role of cuproptosis regulator in diagnosis and subtype of osteoarthritis

作　　者：熊波 王斌[2] 刘金富 陆冠宇 陈财 黄悦 陈莉华 Xiong Bo;Wang Bin;Liu Jinfu;Lu Guanyu;Chen Cai;Huang Yue;Chen Lihua(Graduate School of Guangxi University of Chinese Medicine,Nanning 530299,Guangxi Zhuang Autonomous Region,China;First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学研究生院,广西壮族自治区南宁市530299 [2]广西中医药大学第一附属医院,广西壮族自治区南宁市530023

出　　处：《中国组织工程研究》2023年第34期5530-5537,共8页Chinese Journal of Tissue Engineering Research

基　　金：广西中医药大学校级项目(YCXJ2021070),项目负责人:熊波;广西中医药大学校级项目(YCXJ2021071),项目负责人:黄悦;广西高校中青年教师科研基础能力提升项目(2022KY0282),项目负责人:刘金富。

摘　　要：背景:滑膜在骨关节炎的病程发展过程中发挥着重要作用,而铜死亡是近期最新发现的一种新型细胞程序性死亡,目前尚未有从滑膜角度探究铜死亡基因在骨关节炎中的相关机制研究。目的:以滑膜为切入点从铜死亡角度探究影响骨关节炎发生发展的潜在机制。方法:通过GEO数据库检索符合条件的骨关节炎相关芯片,对其进行标准化处理,基于处理后的基因表达矩阵进行铜死亡相关基因提取和量化,通过随机森林树模型、支持向量机模型、机器学习、列线图模型构建疾病预测模型以预测骨关节炎患病的风险。然后,运用共识聚类算法、主成分分析(PCA)、单样本基因组富集分析(ssGSEA)及免疫浸润分析铜死亡分子亚型与免疫微环境及炎症因子的相关性。结果与结论:(1)首次建立了基于铜死亡特征基因的风险预测模型,由3个铜死亡特征基因(DBT、LIPT1、FDX1)构建的疾病预测模型可以较好预测骨关节炎患病的风险;(2)首次发现骨关节炎患者可分型为两种完全不同的铜死亡分子亚型(族A和族B),族B与Th1/Th2细胞比例失衡高度相关,具有更高的白细胞介素2、白细胞介素4、白细胞介素5表达水平。BACKGROUND:Synovium plays an important role in the development of osteoarthritis,and cuproptosis is a new type of programmed cell death recently discovered,up to now,there is no research on the mechanism of cuproptosis gene in osteoarthritis from synovial angle.OBJECTIVE:The synovial membrane was used as the entry point to explore the potential mechanism of the development of osteoarthritis from the perspective of cuproptosis.METHODS:The coincident osteoarthritis related chips were retrieved through Gene Expression Omnibus(GEO)database and standardized.Cuproptosis related genes were extracted and quantified based on the gene expression matrix after treatment.Random Forest model,Support Vector Machines model,Machine learning and Nomogram Model were used to construct disease prediction model to predict the risk of osteoarthritis.Then,consensus clustering algorithm,principal component analysis,single sample gene set enrichment analysis and immune infiltration were used to analyze the correlation of cuproptosis molecular subtypes with immune microenvironment and inflammatory factors.RESULTS AND CONCLUSION:(1)A risk prediction model based on cuproptosis characteristic gene was established for the first time.The disease prediction model constructed by three cuproptosis characteristic genes(DBT,LIPT1,FDX1)could predict the risk of osteoarthritis.(2)It is found for the first time that patients with osteoarthritis can be classified into two distinct subtypes of cuproptosis molecule(cluster A and cluster B).Cluster B is highly correlated with the imbalance of Th1/Th2 cell ratio,and has higher expression levels of interleukin-2,interleukin-4,and interleukin-5.

关 键 词：膝骨关节炎 铜死亡 预测模型 机器学习 免疫浸润 炎症因子 分子亚型 

分 类 号：R446[医药卫生—诊断学] R318[医药卫生—临床医学] R496