Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is the most diagnosed subtype of lung cancer; ferroptosis is widely involved in the pathological cell death associated with various cancers, including lung cancer. However, the comprehensive relationship between ferroptosis and LUAD is little known in molecular levels until now. In the present study, 513 LUAD patients could be aggregated into three clusters by consensus clustering based on RNA sequencing data of 291 ferroptosis-related genes (FRGs) in The Cancer Genome Atlas (TCGA) database; cluster2 had significant survival advantage compared to the other two clusters. A novel prognostic model of 8 differential FRGs was constructed to effectively divide LUAD patients into high- or low-risk group according to the risk scores by the Cox and LASSO regression analyses. The overall survival of LUAD patients in the high-risk group was significantly worse in the TCGA and GEO cohorts. Moreover, patients with radiation therapy or high clinical stage had obviously higher risk scores. We validated the differential mRNA and protein expression of four FRGs in paired tumor and normal samples from our clinical cohort. Our study constructed a novel FRG signature to predict the prognosis of LUAD patients, which might provide a new prognostic tool and potential therapeutic targets for LUAD.