Development and validation of a combined ferroptosis- and pyroptosis-related gene signatures for the prediction of clinical outcomes in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a very heterogeneous cancer with a bad prognosis. Pyroptosis and ferroptosis are two newly discovered forms of regulated cell death, which can trigger inflammation-related immunosuppression in tumor microenvironments, thereby promoting tumor growth. So far, there has been no thorough systematic investigation of the predictive values of ferroptosis and pyroptosis-related genes in LUAD. Therefore, in this study, we conducted a combined analyses in the gene expression of ferroptosis and pyroptosis and identified four distinct subgroups: immobility, ferroptosis, pyroptosis, and mixed. The gene sets most closely associated to both ferroptosis and pyroptosis were utilized to build a risk prediction model based on their variations in survival and biological activities. More importantly, our conclusions from bioinformatics analyses were validated by external experiments in patients with LUAD. In conclusion, the establishment of LUAD subgroups based on the ferroptosis- and pyroptosis-related gene expression profile provided new insights into understanding the roles of programmed cell death in oncogenesis and might contribute to the development of individualized therapy.