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Research Paper|Volume 16, Issue 18|pp 12608—12622

Characterization of a ferroptosis-related gene signature predicting survival and immunotherapeutic response in lung adenocarcinoma

Chuan Zhang1, Yingying Su2, Hongrui Wang3, Dan Dang4, Xin Huang3, Shuyou Shi3, Yue Shi5, Peng Zhang6, Ming Yang3
  • 1Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, China
  • 2Department of Anatomy, College of Basic Medical Sciences, Jilin University, Jilin, China
  • 3Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, China
  • 4Department of Neonatology, The First Hospital of Jilin University, Changchun, China
  • 5Department of Microbiology and Immunology, Changchun University of Chinese Medicine, Changchun, China
  • 6Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, China
* Equal contribution
Received: July 4, 2023Accepted: July 11, 2024Published: September 18, 2024
https://doi.org/10.18632/aging.206110

Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Lung cancer remains the leading cause of cancer-related death worldwide, and drug resistance represents the main obstacle responsible for the poor mortality and prognosis. Here, to identify a novel gene signature for predicting survival and drug response, we jointly investigated RNA sequencing data of lung adenocarcinoma patients from TCGA and GEO databases, and identified a ferroptosis-related gene signature. The signature was validated in the validation set and two external cohorts. The high-risk group had a reduced survival than the low-risk group (P < 0.05). Moreover, the established gene signature was associated with tumor mutation burden, microsatellite instability, and response to immune checkpoint blockade. In addition, four candidate oncogenes (RRM2, SLC2A1, DDIT4, and VDAC2) were identified to be candidate oncogenes using in silico and wet experiments, which could serve as potential therapeutic targets. Collectively, this study developed a novel ferroptosis-related gene signature for predicting prognosis and drug response, and identified four candidate oncogenes for lung adenocarcinoma.