Fatty acid degradation-related gene signatures as biomarkers for ocular sarcoidosis

Sarcoidosis is characterized by the proliferation of noncaseating granulomas and presents as a complex chronic inflammatory disease. It extensively affects multiple organ systems, with 30-60% of patients experiencing ocular complications, predominantly bilateral granulomatous uveitis. Fatty acid degradation, a fundamental metabolic process, is crucial for cellular energy homeostasis, involving the breakdown of fatty acids to produce acetyl-CoA, NADH, and FADH2, which then enter the citric acid cycle and electron transport chain to generate ATP. Despite its importance, the role of fatty acid degradation genes (FADGs) in the pathophysiology of Ocular sarcoidosis (OS) remains unclear. To identify candidates potentially involved in OS, we intersected differentially expressed genes (DEGs) with a curated list of 177 FADGs. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), were employed to explore biological functions. Further refinement using Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) allowed for the identification of key hub genes and assessment of their diagnostic potential for OS. Our investigation identified two FADGs, ADH1B and ECI1, closely associated with OS. Functional analyses revealed their involvement in processes such as fatty acid metabolic processes, small molecule catabolic processes, and fatty acid oxidation. Importantly, the diagnostic capabilities of these FADGs demonstrated significant efficacy in distinguishing OS from unaffected states. Through rigorous bioinformatics analyses, this study identifies ADH1B and ECI1 as novel biomarker candidates for OS, elucidating their potential roles in the disease's pathogenesis. These findings offer new insights into the molecular mechanisms underlying OS and highlight the diagnostic potential of FADGs in differentiating OS from unaffected conditions.