Shared molecular signatures between systemic lupus erythematosus and osteoporosis

Abstract

This study explores the molecular interplay between systemic lupus erythematosus (SLE) and osteoporosis (OP), aiming to uncover shared gene signatures and pathways for better treatment approaches. Leveraging microarray data from the Gene Expression Omnibus (GEO) database, we employed weighted gene coexpression network analysis to identify coexpression modules in SLE and OP, with subsequent protein–protein interaction analysis clarifying the connections among shared genes. Key genes were pinpointed using CytoHubba and random forest algorithms, validated across independent GEO datasets, and further analyzed through gene set enrichment analysis (GSEA) and immune infiltration studies. We discovered two highly correlated modules in SLE and OP, isolating 30 shared genes and identifying GBP1, SOCS1, IFI16, and XAF1 as central to both conditions. Notably, XAF1 and GBP1 mRNA levels were significantly elevated in the peripheral blood of SLE patients compared with healthy and RA counterparts, underscoring their potential as biomarkers. GSEA and immune infiltration analyses indicated pronounced immune and inflammatory responses, especially in interferon signaling pathways, implicating these core-shared gene networks in the diseases' pathogenesis. The findings highlight the involvement of GBP1, SOCS1, IFI16, and XAF1 in SLE with concurrent OP and suggest that targeting immune and inflammatory responses, particularly through interferon pathways, may offer therapeutic promise for these intertwined conditions.