Exploring the Shared Diagnostic Biomarkers and Molecular Mechanisms Related to Mitochondrial Dysfunction in...

Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are chronic inflammatory diseases that share immune dysregulation and mitochondrial dysfunction. Understanding the molecular mechanisms linking these diseases to mitochondrial dysfunction is crucial for developing novel diagnostic and therapeutic strategies. Datasets related to IBD and RA were obtained from the Gene Expression Omnibus database. Differentially expressed mitochondrial dysfunction-related genes (MDRGs) were identified using differential expression analysis. Weighted gene co-expression network analysis was performed to identify crosstalk genes (CGs). Logistic regression and support vector machine (SVM) models were constructed using least absolute shrinkage and selection operator regression to identify hub genes. Additionally, the differential expression and diagnostic value of the hub genes were verified using quantitative reverse transcriptase-polymerase chain reaction and validation sets. Finally, immune infiltration analysis was conducted to assess the role of immune cells in IBD and RA. A total of 87 CGs associated with mitochondrial dysfunction were identified between IBD and RA, among which PDIA4 and DUSP6 were identified as hub genes. Twenty proteins, including ERO1A, MAPK7, and P4HB, were identified as key proteins that interacted with PDIA4 and DUSP6. The area under the curve (AUC) of the ROC curves for IBD and RA based on the DUSP6 and PDIA4 diagnostic models were 0.664 and 0.856, respectively. The qRT-PCR results indicated that PDIA4 and DUSP6 were overexpressed in IBD and RA. Seven immune cell types, including activated B cells, activated dendritic cells, and eosinophils showed significant differences in the IBD and RA groups. Our findings highlight the close association between IBD, RA, and mitochondrial dysfunction. PDIA4 and DUSP6 may serve as potential biomarkers of mitochondrial dysfunction in patients with IBD and RA.