Large-Scale Transcriptome Analysis Identified Novel Ferroptosis-Related Gene Signatures for Predicting the Prognostic of Patients with Lung Adenocarcinoma

Abstract

Background: Lung cancer is the most common of all malignant tumors. Traditional tumor staging has general sensitivity and specificity in predicting patient prognosis. Ferroptosis is a novel form of non-apoptotic form of cell death promoted by lipid peroxidation. Ferroptosis may be involved in the malignant progression of tumors through the regulation of glutathione depletion or the P53 signaling pathway. However, there are fewer studies on the impact of ferroptosis on tumor prognosis.Methods: We summarized 22 molecules that regulate ferroptosis. The transcriptome and corresponding clinical data were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The Wilcoxon test was utilized to analyze the expression of ferroptosis-related genes. We established risk score signatures, and all patients divided into two groups. Survival curves and multifactorial Cox regression analyses were performed to explore the prognostic value of ferroptosis on lung adenocarcinoma (LUAD).Results: We found that most ferroptosis-related genes are specifically expressed in LUAD tissue. We established a six‑mRNA signature and a seven‑IncRNA signature. All the models showed high predictive performance (AUC: 0.66–0.8), and patients in the low-risk group had higher overall survival than those in the high-risk group (P<0.05). The risk score is an independent risk factor for predicting the prognosis of LUAD.Conclusions: Our study demonstrates the critical role of ferroptosis in LUAD, and it is expected to supply a reference for the prognostic stratification of LUAD.