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Background: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. FBXO43, a member of the F‐box protein family, has been identified as a crucial prognostic factor in several cancers. However, its role in osteosarcoma remains largely unexplored. Methods: This study investigated the expression and potential role of FBXO43 across the TCGA pan‐cancer cohort, with a particular focus on sarcoma (SARC). We analyzed the relationship between FBXO43 expression and various cancer‐related pathways, immune infiltration, and genomic features, including TP53 mutations. We also conducted immunotherapy predictive analyses using TIDE and Submap algorithms. To validate our findings, we performed a series of in vitro experiments, including cell invasion and wound healing assays. Results: FBXO43 was found to be significantly overexpressed in various cancers and was particularly associated with pathways such as E2F_TARGETS and G2M_CHECKPOINT in SARC samples. Differential FBXO43 expression was linked to distinct immune infiltration patterns and pathway enrichments. Notably, high FBXO43 expression in osteosarcoma was associated with a higher TP53 mutation rate. Predictive analyses indicated that patients with low FBXO43 expression had better immunotherapy responses, suggesting its potential as a diagnostic and prognostic biomarker. These findings were corroborated by our in vitro functional assays. Conclusion: Our comprehensive analysis reveals that FBXO43 plays a critical role in the progression of osteosarcoma, impacting both immune infiltration and genomic stability. FBXO43 expression levels may serve as valuable biomarkers for predicting immunotherapy responses in osteosarcoma patients. Future studies should aim to elucidate the molecular mechanisms driving FBXO43's role and validating these findings in clinical settings to develop targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis of the hip or knee has been reported to be linked to an increased risk of frailty. However, a definitive conclusion about whether hip or knee osteoarthritis increases susceptibility to frailty remains elusive. Material and methods: The instrumental variables (IVs) used in this analysis were sourced from publicly available genome-wide association study (GWAS) datasets. We used a two-sample Mendelian randomization analysis to evaluate the plausible causal nexus between hip or knee osteoarthritis and frailty. Results: We included a total of 25 single-nucleotide polymorphisms (SNPs) as instrumental variables through rigorous and comprehensive screening. The results of this analysis suggested that hip or knee osteoarthritis is associated with an elevated risk of frailty. These results remained robust and consistent across multiple calculation methods, including inverse variance weighted (OR = 1.082, 95% CI: 1.0532-1.1125, p = 1.36 × 10-8), MR-Egger regression (OR = 1.175, 95% CI: 1.0162-1.3604, p = 0.040), weighted median estimation (OR = 1.078, 95% CI: 1.0365-1.1219, p = 1.831 × 10-4), weighted mode analysis (OR = 1.089, 95% CI: 1.0078-1.1771, p = 0.041) and simple mode analysis (OR = 1.093, 95% CI: 1.0112-1.1830, p = 0.034). Cochran's Q test showed no evidence of heterogeneity among the IV estimates derived from individual variants, and the MR-Egger regression analysis indicated that the presence of horizontal pleiotropy was unlikely to introduce bias into the results (intercept: -0.0044, p = 0.549). Conclusions: Two-sample Mendelian randomization analysis effectively identified hip or knee osteoarthritis as a contributing risk factor for frailty. [ABSTRACT FROM AUTHOR]