Plasma proteins and osteosarcoma risk: causal evidence from Mendelian randomization

Osteosarcoma (OS) is an exceptionally aggressive bone cancer, and the identification of blood-based biomarkers for early detection and prognosis remains a significant challenge. This study aimed to investigate the causal relationships between circulating plasma proteins and OS risk using Mendelian randomization (MR). We utilized genome-wide association study (GWAS) summary statistics, which included 3,282 plasma protein traits from the IEU Open GWAS Project and the FinnGen consortium. Our MR analysis identified 59 proteins positively associated with OS risk, while 66 proteins were inversely associated. Notably, Lactoylglutathione lyase, also known as Glyoxalase 1 (GLO1), showed a significant protective effect on OS risk (IVW OR = 0.2871, 95% CI: 0.1602-0.5145, P = 2.7580 × 10^{- 5}). After false discovery rate (FDR) correction, this association remained significant (FDR_pavl < 0.1). These findings emphasize the potential of circulating proteins, particularly GLO1, as biomarkers for OS, reflecting its role in oxidative stress and inflammation regulation. The study underscores the importance of proteomic analysis in OS pathogenesis and suggests the need for further investigation to validate these associations and explore potential therapeutic targets, thereby providing new insights into the biological mechanisms of OS.