Proteomic analysis reveals biomarkers associated with performance-based joint function and patient-reported outcomes in knee osteoarthritis

Objective: This study aimed to identify proteins associated with clinical manifestations of knee osteoarthritis (KOA), including performance-based joint function and patient-reported outcome measures (PROM). Methods: This cross-sectional exploratory study included thirteen individuals with KOA and eleven age-matched controls. All participants performed the 30s Single Leg Mini Squat test and 30s Sit-to-Stand test with simultaneous recording of joint kinematics. Individuals with KOA completed the Knee Injury and Osteoarthritis Outcome Score and Forgotten Joint Score-12. Proteins were determined by quantitative mass spectrometry (MS) in plasma. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and Reactome enrichment analysis of the proteome were conducted to identify activated pathways and groups. Results: Performance-based function was worse in individuals with KOA compared to controls, and they reported higher levels of pain. MS analysis identified 82 differentially expressed proteins (DEPs) in KOA (28 upregulated, 54 downregulated of 321 detected proteins). PCA displayed distinct features between KOA and controls, similar to HCA, which distinguished two major clusters. Enrichment analysis displayed platelet activation and degranulation, neutrophil, and extracellular matrix (ECM)-related pathways. From the proteome, 23 DEPs were associated with different aspects of joint function, and 25 DEPs with PROM. Conclusions: Individuals with KOA differed from controls across all three assessment modalities; they presented worse joint function, higher levels of pain, and an altered plasma protein profile. Multiple associations were observed between up- and downregulated DEPs and clinical manifestations. The described study protocol shows promise for performing multivariate analyses for future subgrouping of individuals with KOA.