Identification of potential biomarkers and immunoregulatory mechanisms of rheumatoid arthritis based on multichip co-analysis of GEO database
10.12122/j.issn.1673-4254.2024.06.10
- VernacularTitle:类风湿关节炎的潜在生物标志物及其免疫调控机制:基于GEO数据库
- Author:
Lili CHEN
1
;
Tianyu WU
;
Ming ZHANG
;
Zixia DING
;
Yan ZHANG
;
Yiqing YANG
;
Jiaqian ZHENG
;
Xiaonan ZHANG
Author Information
1. 蚌埠医科大学 卫生管理学院,安徽 蚌埠,233030
- Keywords:
rheumatoid arthritis;
biomarkers;
immune regulatory;
bionformatic;
machine learning
- From:
Journal of Southern Medical University
2024;44(6):1098-1108
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.
