Abstract

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.

Highlights

  • IntroductionLung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the world, with 2.1 million new cases and 1.8 million deaths predicted in 2018 [1]

  • Phenotype, and full clinical annotation of 526 Lung adenocarcinoma (LUAD) patients were obtained from the The Cancer Genome Atlas (TCGA) database

  • To assess the biological functions of ferroptosis in the progression of LUAD, we investigated the expression patterns of 291 ferroptosis-related genes (FRGs) which were mainly selected from the FerrDb database

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Summary

Introduction

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in the world, with 2.1 million new cases and 1.8 million deaths predicted in 2018 [1]. Lung adenocarcinoma (LUAD) is the most diagnosed subtype of NSCLC, followed by lung squamous cell carcinoma (LUSC) [4]. LUAD is associated with distinct genomic alterations and widespread molecular heterogeneity compared with other lung cancer subtypes [4]. Substantial progress in the treatment of lung cancer have been achieved over the past decades, the 5-year survival rate of lung cancer patients remains only 4%–17% depending on stage and regional differences [5]. It is important to Ferroptosis-Related Prognostic Model for LUAD identify novel prognostic biomarkers and develop an effective prognostic model for predicting the survival of LUAD patients

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