2. Academic Validation
  3. Ferroptosis-related gene signature for predicting prognosis and identifying potential therapeutic drug in EGFR wild-type lung adenocarcinoma

Ferroptosis-related gene signature for predicting prognosis and identifying potential therapeutic drug in EGFR wild-type lung adenocarcinoma

  • Commun Biol. 2024 Oct 30;7(1):1416. doi: 10.1038/s42003-024-07117-1.
Chuankai Zhang # 1,  Qi Wu # 2,  Hongwei Yang # 2,  Hui Zhang 2,  Changqing Liu 3,  Bo Yang 4,  Qingsong Hu 5 6
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zhangchuankai@ustc.edu.cn.
  • 2 Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China.
  • 3 Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • 4 The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. yangbo6674@163.com.
  • 5 Department of Thoracic Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. qshu@ustc.edu.cn.
  • 6 Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China. qshu@ustc.edu.cn.
  • # Contributed equally.
PMID: 39478024 DOI: 10.1038/s42003-024-07117-1
Abstract

Epidermal growth factor receptor wild type lung adenocarcinoma (EGFRWT 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 EGFRWT 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 FeSighigh patients causing tumor resistance to Ferroptosis. To address this challenge, we screened potential drugs from NCI-60 (The US National Cancer Institute 60 human tumour cell line Anticancer drug screen) and Connectivity map database, ultimately identifying 6-mercatopurine (6-MP) as a promising candidate. Both in vitro and in vivo experiments demonstrated its efficacy in treating FeSighigh EGFRWT LUAD tumor models. In summary, we develop a novel FeSig for predicting prognosis and guiding drug application.

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