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Abstract

This study focused on elucidating the role of PANoptosis in Osteosarcoma (OS), a highly malignant bone tumor. By screening and integrating OS-related microarray datasets from Gene Expression Omnibus (GEO), we identified 105 PANoptosis-related differentially expressed genes (OS_PAN_DEGs) primarily involved in apoptosis, necroptosis, proteasome, hippo signaling, and neurodegenerative disease pathways. These genes were used to classify OS into three distinct subtypes with varying clinical outcomes, immune characteristics, and mutational landscapes. Additionally, we developed an OS_PAN index model to assess the association between PANoptosis and OS features, treatment response, and prognosis. Notably, high OS_PAN-index patients responded well to immunotherapy, while low-index patients showed sensitivity to small-molecule targeted drugs. Drug screening revealed Pazopanib, Chelerythrine, Staurosporine, Hydroxyurea, and Sunitinib as potential therapeutic agents positively correlated with OS_PAN_DEGs expression. This comprehensive analysis enhances our understanding of OS pathogenesis and offers novel therapeutic targets for OS treatment.

Keywords: Osteosarcoma (OS); PANoptosis; Immune characteristics; Drug sensitivity; Prognostic index