Elucidating the multifaceted roles of GPR146 in non-specific orbital inflammation: a concerted analytical approach through the prisms of bioinformatics and machine learning

• DOI: 10.3389/fmed.2024.1309510
• Publication Date: 2024-06-05T05:03:16Z
• Authors: Zixuan Wu; Ling Li; Tingting Xu; Yi Hu; Xin Peng; Zheyuan Zhang; Xiaolei Yao; Qinghua Peng
• Keywords: Medicine (General); 0303 health sciences; 03 medical and health sciences; R5-920; Medicine; non-specific orbital inflammation (NSOI); LASSO regression; autoimmune inflammatory disorder; GPR146; SVM-RFE

Background Non-specific Orbital Inflammation (NSOI) is a chronic idiopathic condition marked by extensive polymorphic lymphoid infiltration in the orbital area. The integration of metabolic and immune pathways suggests potential therapeutic roles for C-peptide G protein-coupled receptor 146 (GPR146) diabetes its sequelae. However, specific mechanisms through which GPR146 modulates responses remain poorly understood. Furthermore, utility as diagnostic or prognostic marker NSOI has not been conclusively demonstrated. Methods We adopted comprehensive analytical strategy, merging differentially expressed genes (DEGs) from Gene Expression Omnibus (GEO) datasets GSE58331 GSE105149 with immune-related ImmPort database. Our methodology combined LASSO regression support vector machine-recursive feature elimination (SVM-RFE) selection, followed Set Enrichment Analysis (GSEA) Variation (GSVA) to explore gene sets co-expressed GPR146, identifying significant enrichment pathways. tumor microenvironment’s composition was quantified using CIBERSORT algorithm ESTIMATE method, confirmed positive correlation between expression cell infiltration. Validation performed dataset. Results identified 113 DEGs associated subset showing distinct patterns. Using SVM-RFE, we pinpointed 15 key hub genes. Functionally, these were predominantly linked ligand activity, cytokine-mediated signaling. Specific cells, such memory B M2 macrophages, resting mast monocytes, activated NK plasma CD8+ T positively expression. In contrast, M0 naive M1 CD4+ gamma delta cells showed inverse correlations. Notably, our findings underscore relevance distinguishing NSOI. Conclusion study elucidates immunological signatures context NSOI, highlighting potential. These insights pave way be novel biomarker monitoring progression providing foundation future strategies targeting immune-metabolic