Comprehensive Analysis of FBXO43 Expression and Its Prognostic and Therapeutic Implications in Osteosarcoma

Abstract

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.