Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma

Guangxu Tu; Weilin Peng; Qidong Cai; Zhenyu Zhao; Xiong Peng; Boxue He; Pengfei Zhang; Shuai Shi; Yongguang Tao; Xiang Wang

doi:10.7717/peerj.11687

Construction and validation of a 15-gene ferroptosis signature in lung adenocarcinoma

PeerJ. 2021 Jul 7:9:e11687. doi: 10.7717/peerj.11687. eCollection 2021.

Authors

Guangxu Tu^{1

2}, Weilin Peng^{1

2}, Qidong Cai^{1

2}, Zhenyu Zhao^{1

2}, Xiong Peng^{1

2}, Boxue He^{1

2}, Pengfei Zhang^{1

2}, Shuai Shi^{1

2}, Yongguang Tao^{3

4}, Xiang Wang^{1

2}

Affiliations

¹ Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan, China.

Abstract

Background: Ferroptosis is a novel form of programmed cell death characterized by the excessive accumulation of intracellular iron and an increase in reactive oxygen species. Emerging studies have shown that ferroptosis plays a vital role in the progression of lung adenocarcinoma, but the effect of ferroptosis-related genes on prognosis has been poorly studied. The purpose of this study was to explore the prognostic value of ferroptosis-related genes.

Methods: Lung adenocarcinoma samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to establish a predictive signature for risk stratification. Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curve analysis were conducted to evaluate the signature. We further explored the potential correlation between the risk score model and tumor immune status.

Results: A 15-gene ferroptosis signature was constructed to classify patients into different risk groups. The overall survival (OS) of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The signature could predict OS independent of other risk factors. Single-sample gene set enrichment analysis (ssGSEA) identified the difference in immune status between the two groups. Patients in the high-risk group had stronger immune suppression, especially in the antigen presentation process.

Conclusions: The 15-gene ferroptosis signature identified in this study could be a potential biomarker for prognosis prediction in lung adenocarcinoma. Targeting ferroptosis might be a promising therapeutic alternative for lung adenocarcinoma.

Keywords: Ferroptosis; Immune status; Lung adenocarcinoma; Prognostic signature.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 82072594), the Hunan Provincial Key Area R&D Programmes (No. 2019SK2253) and the Fundamental Research Funds for the Central Universities of Central South University (No. 2021zzts0385). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.