Multi-Omics Identifies Angiogenesis and Lipid Metabolic Pathways Were Associated with Early Revision after Total Joint Arthroplasty in Osteoarthritis Patients

Objectives To identify molecular pathways and key proteins associated with early revision after total joint arthroplasty (TJA) in osteoarthritis (OA) patients using a multi-omics approach integrating plasma proteomics and metabolomics. Methods Primary OA patients who underwent total knee or hip arthroplasty were included. Plasma proteomic profiling was performed using the Olink® Explore HT platform, and plasma metabolomic profiling was conducted using the Biocrates MxP Quant 500 kit. Associations between early revision after TJA and protein expression were evaluated using logistic regression adjusted for age, sex, and body mass index. Functional enrichment analysis was conducted using KEGG and GO databases. Protein-protein interaction network was constructed via the STRING database, visualized in Cytoscape 3.10.4, and hub proteins were identified using the CytoHubba plug-in. Metabolites associated with hub proteins were identified using Spearman correlation analysis. Bonferroni correction was applied for multiple testing (α=9.23×10^-6 for 5,416 proteins; α=2.70×^10-5 for 622 metabolites and 3 hub proteins). Results A total of 168 patients were included, with revision data extracted an average of 10.5 years after primary TJA. The early revision rate was 3% (Figure 1A), with a mean time to revision of 2.6 years. No individual protein reached significance after multiple testing correction. However, 337 proteins were nominally associated with early revision (p<0.05). These proteins were enriched in complement and coagulation cascades, hematopoietic cell lineage, and regulation of angiogenesis and vasculature development pathways (Figure 1B,C). FLT3, IL10, and NRAS were identified as hub proteins (Figure 1D), among which FLT3 and NRAS were negatively associated with early revision TJA, while IL10 was positively associated. Although no metabolite reached multiple-testing corrected significance, 28, 17, and 18 metabolites were nominally correlated (p<0.05) with FLT3, IL10, and NRAS, respectively, predominantly long-chain diglycerides, triglycerides, and phosphatidylcholines. Figure 1 Conclusion Multi-omics integration of plasma proteomics and metabolomic data revealed that dysregulation of angiogenesis and lipid metabolic pathways may contribute to the risk of early revision TJA in patients with primary OA. These pathways and their key molecular mediators warrant further validation as potential predictive biomarkers or therapeutic targets.