Establishment and Validation of a Ferroptosis-Related Gene Signature to Predict Overall Survival in Lung Adenocarcinoma

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common and lethal subtype of lung cancer. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a target in cancer therapy. However, the prognostic value of ferroptosis-related genes (FRGs)x in LUAD remains to be explored. Methods: In this study, we used RNA sequencing data and relevant clinical data from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) dataset to construct and validate a prognostic FRG signature for overall survival (OS) in LUAD patients and defined potential biomarkers for ferroptosis-related tumor therapy. Results: A total of 86 differentially expressed FRGs were identified from LUAD tumor tissues versus normal tissues, of which 15 FRGs were significantly associated with OS in the survival analysis. Through the LASSO Cox regression analysis, a prognostic signature including 11 FRGs was established to predict OS in the TCGA tumor cohort. Based on the median value of risk scores calculated according to the signature, patients were divided into high-risk and low-risk groups. Kaplan–Meier analysis indicated that the high-risk group had a poorer OS than the low-risk group. The area under the curve of this signature was 0.74 in the TCGA tumor set, showing good discrimination. In the GEO validation set, the prognostic signature also had good predictive performance. Functional enrichment analysis showed that some immune-associated gene sets were significantly differently enriched in two risk groups. Conclusion: Our study unearthed a novel ferroptosis-related gene signature for predicting the prognosis of LUAD, and the signature may provide useful prognostic biomarkers and potential treatment targets.