Department of Rheumatology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Immunol. 2022 May 6;13:865425. doi: 10.3389/fimmu.2022.865425. eCollection 2022.
Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein-protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8T cell, and natural killer cell in the pathological mechanism, which can be better utilized for future research on RA. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.
类风湿关节炎(RA)导致严重残疾和生产力损失,因此迫切需要合适的生物标志物用于诊断、治疗评估和预后评估。为了鉴定 RA 的血清标志物,我们采用基于质谱(MS)的蛋白质组学技术,使用随机森林机器学习模型和 11 种蛋白质-蛋白质相互作用(PPI)网络拓扑分析方法,在正常人和 RA 患者样本中获得了 24 个重要的标志物。我们使用额外的蛋白质组学数据集、免疫浸润状态、组织特异性、亚细胞定位、与基于疾病活动的诊断指标的相关性分析以及诊断接收者操作特征分析对标志物进行了重新分析。我们发现血清中的 ORM1 在正常人和 RA 患者样本中的表达存在显著差异,与疾病活动呈正相关,与病理机制中的 CD56dim 自然杀伤细胞、效应记忆 CD8T 细胞和自然杀伤细胞密切相关,这可以为未来的 RA 研究提供更好的利用价值。本研究为发现 RA 的潜在血清生物标志物提供了一种全面的策略,并为理解 RA 的病理机制、识别潜在治疗靶点和疾病管理提供了不同的视角。