ArticleClinical rheumatology2026
Expression and clinical significance of fatty acid metabolism-related genes in PBMCs of SSc patients.
Article in Clinical rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeBioinformatic analysis of fatty acid metabolism-related genes (FAMRGs) in systemic sclerosis (SSc) patients' peripheral blood mononuclear cell (PBMC) expression profiles and clinical significance analysis provides SSc pathogenesis insights. PATIENTS AND
methodsThe study used GSE22356 and GSE33463 datasets from the GEO database to identify fatty acid metabolism-related genes (FAMRGs) in SSc via GSEA and WGCNA. Then, RT-qPCR validated their expression and analyzed the correlation between FAMRGs and clinical data/lipid levels. Lastly, it assessed the diagnostic value of FAMRGs for SSc comorbidities using ROC curve analysis.
resultsGSEA of SSc datasets found fatty acid metabolism enrichment. WGCNA identified SSc-correlated modules and genes. Cross-analysis with MSigDB revealed five SSc-associated FAMRGs (HIBCH, ACADM, IDH1, ACOX1, SUCLA2). Clinical data showed SSc patients had higher TG, WBC, and GR and lower TC, HDL-c, Hb, and LY than HC (p < 0.05). Subgroup analysis found SSc-ILD-PAH had higher age and ESR but lower Hb and LDL-c than SSc-ncILD-ncPAH (p < 0.05). RT-qPCR showed that HIBCH, ACADM, and ACOX1 were upregulated in SSc. ACADM and ACOX1 were higher in SSc-ILD-ncPAH. ACADM negatively correlated with TC and HDL-C (r = - 0.383, p = 0.028; r = - 0.372, p = 0.033). ROC analysis showed ACADM and ACOX1 had AUC values of 0.682 and 0.672 in diagnosing SSc-ILD. SSc-ILD-PAH had higher HIBCH and ACOX1 than SSc-ILD-ncPAH.
conclusionThe expression of fatty acid metabolism-related genes (HIBCH, ACADM, and ACOX1) is different in SSc patients' PBMCs. HIBCH may help in SSc-ILD-PAH diagnosis. Fatty acid metabolism dysregulation and lipid level changes in SSc patients are linked to immune dysfunction and chronic inflammation, impacting disease progression. Key Points • This study identified five pivotal fatty acid metabolism-related genes (FAMRGs) (HIBCH, ACADM, ACOX1, IDH1, and SUCLA2) in systemic sclerosis (SSc) patients through integrated bioinformatics analysis, combining Gene Expression Omnibus (GEO) data retrieval, Gene Set Enrichment Analysis (GSEA), and Weighted Gene Co-Expression Network Analysis (WGCNA). • This study revealed that FAMRGs such as HIBCH, ACADM, and ACOX1 were significantly upregulated in peripheral blood mononuclear cells (PBMCs) of SSc patients, suggesting that dysregulated fatty acid metabolism may be implicated in the pathogenesis of SSc. • The expression levels of these genes (HIBCH, ACADM, ACOX1) are significantly correlated with lipid metabolism indicators (e.g., cholesterol, triglycerides) and disease complications (e.g., pulmonary fibrosis) in SSc patients, providing potential targets for metabolic intervention in SSc.
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