MEF2C is a potential prognostic biomarker for osteosarcoma.

The purpose of this study was to investigate potential therapeutic targets for osteosarcoma (OS) and offer hints regarding genetic factors for OS treatment using a bioinformatics method. This study processed 3 OS datasets from the gene expression omnibus database using R software, screening for differentially expressed genes (DEGs). After enrichment analysis, based on expression quantitative trait loci data and the genome-wide association study data of OS, Mendelian randomization analysis was used to screen the genes closely related to OS disease, which intersect with DEGs to obtain co-expressed genes, validation datasets were employed to verify the results. Finally, the roles of co-expressed genes in OS were investigated through multiple bioinformatics methods. In this study, 269 DEGs (156 up-regulated genes and 113 down-regulated genes) were identified. Enrichment analyses indicated that DEGs play important roles in functions and pathways such as extracellular matrix organization, ossification, response to transforming growth factor beta, human T-cell leukemia virus 1 infection, and focal adhesion; Mendelian randomization analyses yielded 1 CEG that was significantly associated with OS (MEF2C). Validation analysis confirmed that MEF2C expression was significantly elevated in OS tissues, aligning with our differential expression results. Gene set enrichment analysis results indicated that MEF2C expression levels may correlate with alterations in biological activities pertinent to the regulation of skeletal system development and mineralization, as well as the enhancement and modulation of immune responses. Immune-cell-related analysis revealed a negative connection between MEF2C and dendritic cells activated. Clinical correlation analysis demonstrated a significant connection between MEF2C and patients with high-risk grade OS (P = .044). Survival analysis demonstrated MEF2C's prognostic value for overall survival in lower-extremity OS (P = .02) and event-free survival (EFS) in both overall OS (P = .008) and lower-extremity subgroups (P = .007). Protein-protein interaction (PPI) network analysis showed that the effect of MEF2C on OS may be related to genes such as APOE and SOX18. The results of this study suggest that MEF2C is associated with an increased risk of OS and that MEF2C has the potential to be a prognostic biomarker for OS.