Disulfidoptosis-related molecular subtypes and prognostic model for optimizing drug therapy in metastatic...

Disulfidotosis is a newly identified form of cell death associated with tumor response, patient outcomes, and cancer progression. This study aims to identify disulfidptosis-related genes (DiRGs) and their role in osteosarcoma (OS) to predict prognosis and optimize drug therapy for better patient survival. Gene expression matrices and clinical information on OS were obtained from the TARGET and GEO databases. Unsupervised clustering analysis identified two DiRG molecular subgroups with significantly different intratumoral heterogeneity and tumor microenvironment cell infiltrating characteristics in OS. A robust disulfidptosis-related prognostic model using five DiRGs was developed, demonstrating excellent predictive and prognostic power in OS with AUC values of 0.69, 0.78, and 0.85 for 1-, 3-, and 5-year periods, respectively. Investigations into the impact of disulfidoptosis on immune status in OS patients across different risk subgroups revealed that a low immune score and compromised immune status were associated with an unfavorable prognosis for OS patients. INF2 and MEGF10 genes are highly reliable predictors of metastasis among the hub DiRG genes. The validation results indicate a robust correlation between the expression of INF2 and MEGF10 and the severity of malignancy and metastasis in OS. Six drugs targeting osteosarcoma metastasis were identified, with INF2-BP-1-102 and MEGF10-AS703569 showing the best docking scores, indicating their potential to treat OS metastasis effectively. These findings provide valuable insight into improving treatment for OS patients.