Evaluation of the expression level of apoptosis and ferroptosis cell death pathways genes in patients with osteosarcoma

Abstract

BackgroundThe osteosarcoma management and failure in tumor removal remain a diagnostic challenge. ObjectivesThe expression pattern of main mediators of apoptosis and ferroptosis cell death pathways and their relevance to tumor severity and response to chemotherapy were surveyed in the current study. MethodsThe mRNA expression level of Bax, Bcl-2, caspase-8, caspase-9, TfR1, and Gpx4 were assessed in 210 bone tissue samples including benign and malignant osteosarcoma tumors and normal bone tissues via Real-time PCR. The correlation between gene expression level and patient's demographic features and the regression analysis was performed. ResultsDown-regulation of Bax, caspase-8, caspase-9, and Gpx4 was observed in bone tumors that were more prominent in high-grade, metastatic, and recurrent malignant tumors. In tumors of patients with no history of chemotherapy, lower expression of caspase-8, caspase-9 and Gpx4 and higher TfR1 expression levels were detected, indicating that ferroptosis might be selected as a substitute cell death pathway to eliminate cancer cells in osteosarcoma. The difference between malignant and benign tumors was not remarkable; while each malignant and benign tumor group compared to their adjacent normal bone tissue showed a significant reduction in the expression level of Bax, caspase-8, caspase-9, and Gpx4. The higher expression of Bcl-2, as an anti-apoptotic mediator was detected in high-grade, and metastatic osteosarcoma tumors. Also, a higher expression level of TfR1 was detected in malignant, high-grade and metastatic osteosarcoma tumors.Also, the metastatic status of malignant tumors was effective in predicting Bax, Bcl-2, Gpx4, and TfR1 expression patterns in osteosarcoma tumors. ConclusionIn osteosarcoma tumors, ferroptosis might be executed as an alternative death pathway while tumors show developing resistance to chemotherapy or when the predominant apoptotic cell death is down-regulated.