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.
Highlights
Lung cancer is the leading cause of cancer-related lethality around the world, with almost 1.6 million deaths per year, and the 5-year survival rate still lags at below 20% (Uras et al, 2020)
A total of 86 differentially expressed ferroptosis-related genes (FRGs) were identified from Lung adenocarcinoma (LUAD) tumor tissues versus normal tissues, of which 15 FRGs were significantly associated with overall survival (OS) in the survival analysis
Based on the median value of risk scores calculated according to the signature, patients were divided into high-risk and low-risk groups
Summary
Lung cancer is the leading cause of cancer-related lethality around the world, with almost 1.6 million deaths per year, and the 5-year survival rate still lags at below 20% (Uras et al, 2020). Lung adenocarcinoma (LUAD) represents the most common subtype of lung cancer, accounting for ∼50% of all cases (Chen et al, 2020). Some risk factors such as smoking, family history of lung cancer, aging, and virus infection have been implicated in the initiation and progression of LUAD (Nakhaie et al, 2020), and molecules and pathways mediating the occurrence and development of LUAD have been continuously investigated (Wang et al, 2020; Zhou et al, 2020). The exploration of other forms of cell death to uncover new biomarkers and targets for LUAD is urgently required. The prognostic value of ferroptosis-related genes (FRGs)x in LUAD remains to be explored
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