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通过整合生物信息学和机器学习对骨关节炎诊断生物标志物及免疫细胞浸润特征进行分析与验证

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in osteoarthritis by integrating bioinformatics and machine learning.

作者信息

Li Tianyang, Wei Jinpeng, Wu Hua, Chen Chen

机构信息

Department of Orthopedics, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.

出版信息

Front Immunol. 2025 Aug 20;16:1596912. doi: 10.3389/fimmu.2025.1596912. eCollection 2025.

Abstract

OBJECTIVE

Exosomes as important carriers of intercellular communication have frequently appeared in recent studies related to osteoarthritis (OA), while the specific mechanism of exosome action in osteoarthritis remains unclear. The aim of this study was to identify potential exosome-related biomarkers in osteoarthritis, to explore the role and mechanism of exosome-related genes in articular cartilage.

METHODS

The data on exosome related genes and normal and OA cartilage genes were obtained through online databases. The potential mechanisms of these genes were revealed by multiple gene enrichment analysis algorithms. Machine learning methods were utilized to identify exosome-related differential genes (ERDEGs) with highly correlated OA features (Hub OA-ERDEGs). In addition, we created a nomogram to assess the ability of Hub OA-ERDEGs to diagnose OA. Single-sample gene set enrichment analysis (ssGSEA) was used to observe the infiltration characteristics of immune cells in OA and their relationship with Hub OA-ERDEGs.

RESULTS

The results of screening Hub OA-ERDEGs using machine learning algorithms show that: TOLLIP, ALB, HP, RHOBTB3, GSTM2, S100A8 and AKR1B1 were significantly up-regulated or down-regulated in OA samples and verified by qRT- PCR for validation. Using the ssGSEA algorithm, we discovered that 8 types of immune cell infiltration and 5 types of immune cell activation.

摘要

目的

外泌体作为细胞间通讯的重要载体,在近期有关骨关节炎(OA)的研究中频繁出现,而外泌体在骨关节炎中的具体作用机制仍不清楚。本研究的目的是鉴定骨关节炎中潜在的外泌体相关生物标志物,探讨外泌体相关基因在关节软骨中的作用及机制。

方法

通过在线数据库获取外泌体相关基因以及正常和骨关节炎软骨基因的数据。采用多种基因富集分析算法揭示这些基因的潜在机制。利用机器学习方法鉴定与骨关节炎特征高度相关的外泌体相关差异基因(枢纽骨关节炎-外泌体相关差异基因)。此外,我们创建了列线图以评估枢纽骨关节炎-外泌体相关差异基因诊断骨关节炎的能力。采用单样本基因集富集分析(ssGSEA)观察骨关节炎中免疫细胞的浸润特征及其与枢纽骨关节炎-外泌体相关差异基因的关系。

结果

使用机器学习算法筛选枢纽骨关节炎-外泌体相关差异基因的结果表明:TOLLIP、ALB、HP、RHOBTB3、GSTM2、S100A8和AKR1B1在骨关节炎样本中显著上调或下调,并通过qRT-PCR进行验证。使用ssGSEA算法,我们发现了8种免疫细胞浸润和5种免疫细胞激活。

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