biostudies-literatureZhang CNatural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation)1416https://www.ebi.ac.uk/biostudies/studies/S-EPMC11525656biostudies-literatureUnknown7(1)Epidermal growth factor receptor wild type lung adenocarcinoma (EGFR^WT LUAD) still has limited treatment options and unsatisfactory clinical outcomes. Ferroptosis, as a form of cell death, has been reported to play a dual role in regulating tumor cell survival. In this study, we constructed a 3-ferroptosis-gene signature, FeSig, and verified its accuracy and efficacy in predicting EGFR^WT LUAD prognosis at both the RNA and protein levels. Patients with higher FeSig scores were found to have worse clinical outcomes. Additionally, we explored the relationship between FeSig and tumor microenvironment, revealing that enhanced interactions between fibroblasts and tumor cells in FeSig^high patients causing tumor resistance to ferroptosis. To address this challenge,Communications biologyFerroptosis-related gene signature for predicting prognosis and identifying potential therapeutic drug in EGFR wild-type lung adenocarcinoma.PMC115256562208085MH237 2208085MH241Yang HWu QZhang HYang BLiu CZhang CHu QfalseFerroptosis-related gene signature for predicting prognosis and identifying potential therapeutic drug in EGFR wild-type lung adenocarcinoma.Epidermal growth factor receptor wild type lung adenocarcinoma (EGFR^WT LUAD) still has limited treatment options and unsatisfactory clinical outcomes. Ferroptosis, as a form of cell death, has been reported to play a dual role in regulating tumor cell survival. In this study, we constructed a 3-ferroptosis-gene signature, FeSig, and verified its accuracy and efficacy in predicting EGFR^WT LUAD prognosis at both the RNA and protein levels. Patients with higher FeSig scores were found to have worse clinical outcomes. Additionally, we explored the relationship between FeSig and tumor microenvironment, revealing that enhanced interactions between fibroblasts and tumor cells in FeSig^high patients causing tumor resistance to ferroptosis. To address this challenge,2024-01-01T00:00:00Z2024 Oct2026-06-02T18:37:51.796Z2025-04-04T00:29:24.314ZS-EPMC115256563947802410.1038/s42003-024-07117-1