Abstract
Osteosarcoma (OS) is a highly prevalent bone tumor derived from primitive mesenchymal cells that occurs mostly in adolescents and children. OS has a notable propensity for aggressive behavior and resistance to treatment. Additionally, accurately evaluating and predicting the prognosis of OS remains challenging. For this investigation, we utilized scRNA-seq data to identify seven subtypes of OS cells. Survival analysis of each OS cell subtype revealed that highly invasive OS (HIS-OS) had a poorer prognosis. Through differential expression analysis, an entire set of seven genes linked to HIS-OS was identified. Subsequently, these seven genes were employed to construct a predictive model using the LASSO approach. Based on the median risk score, the OS samples in the training set were categorized into high-risk and low-risk groups, and the high-risk group exhibited a significantly shorter survival time. The analysis of immunotherapy and anticancer treatment responsiveness indicated a negative correlation between HIS-OS-related gene signatures and immune checkpoints as well as chemotherapy sensitivity. In addition, functional analysis demonstrated high enrichment of these gene sets throughout the process of tumor invasion. Finally, SERPINE2 was identified as a therapeutically critical gene. Therefore, we subsequently selected an inhibitor, IITZ-01, that targets SERPINE2, and we performed molecular docking simulations. Furthermore, we validated the inhibitory effect of IITZ-01 on OS at the cellular level. The results suggest that HIS-OS-related genes are important for prognostic stratification and therapeutic strategies for OS.