Construction and validation of an osteosarcoma prognostic model reveals that SERPINE2 contributes to the progression and cisplatin sensitivity in osteosarcoma.

Osteosarcoma (OS) is a common malignant tumor which lacks robust biomarkers for prognosis and treatment stratification. This research aims to construct a predictive gene signature in OS with prognostic and therapeutic implications. We downloaded from TARGET-OS and GEO databases and obtained 298 differentially expressed genes (DEGs) by analysis of variance. The prognosis model, including multiple genes, was successfully constructed. We identified three molecular subtypes with distinct phenotypes, immune microenvironment profiles, and pathway enrichment patterns. The characteristics of the prognostic model included seven genes (FRZB, MX1, PTN, GRP, ITK, MYC, SERPINE2). Among these genes, SERPINE2 was prioritized for experimental validation; SERPINE2 knockdown suppressed osteosarcoma cell growth and invasion and increased cisplatin-induced DNA damage. Collectively, our results support an integrative prognostic model for OS and suggest SERPINE2 as a candidate modulator of tumor progression and cisplatin resistance.