Development and validation of a novel prognostic and for osteosarcoma patients utilizing multiple organelle related genes

Organelles have been reported to be closely associated with tumor development and progression, but their role in osteosarcoma (OS) remains largely unexplored. Organelle related genes (ORGs) associated with OS prognosis were identified using Cox regression analysis. A prognostic model was subsequently constructed through multivariate Cox regression analysis and validated using an independent dataset. Patients were stratified into high-risk and low-risk groups based on the median risk score. In addition, immune infiltration analysis, enrichment analysis and drug sensitivity evaluation were performed. Finally, in vitro experiments were conducted to validate the potential roles of ORGs in OS. We identified 3 ORGs (ACSS2, CLTCL1, and PLD3) that were significantly associated with OS prognosis. A novel 3 ORG signature was established, which effectively stratified patients into high-risk and low-risk groups with distinct survival outcomes. This signature served as an independent prognostic factor. The areas under the receiver operating characteristic (ROC) curve for the 1-, 4-, and 7-year survival rates were 0.66, 0.74, and 0.83, respectively. These findings were further validated using the independent GSE21257 dataset, where the corresponding ROC curve values for the 1-, 4-, and 7-year survival rates were 0.71, 0.80, and 0.68, respectively. Drug sensitivity analysis revealed differential responses to 4 drugs between the risk groups, with the 3 ORGs (ACSS2, CLTCL1 and PLD3) showing positive correlations with 2 drugs (BI_2536, Dactinomycin). Additionally, functional experiments confirmed the role of ACSS2 in OS cell behavior. This novel ORG signature not only provides a valuable tool for patient stratification but also offers insights into the biological processes driving OS progression and potential therapeutic targets.