Furthermore, ROS fluorescence detection results indicated that the strong ROS fluorescence signal observed in NC group was significantly diminished in 143B co-cultured with CAFs exosomes transfected with OE plasmids (Figure 8E; Supplementary Figure S8, P < 0.001), thereby confirming that the COX4I2 protein derived from CAFs exosomes promoted the malignant proliferation of osteosarcoma cells by inhibiting ferroptosis. The gene discussed is COX4I2; the disease is osteosarcoma.