Abstract

We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan–Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.

Highlights

  • ‘Ferroptosis’ is a type of iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy

  • The validation set was composed of 341 non-small-cell lung cancer (NSCLC) patients from the International Cancer Genome Consortium (ICGC) database

  • A total of 1164 ferroptosis-related genes were obtained from National Center for Biotechnology Information (NCBI) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases and were intersected with DEGS obtained previously

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Summary

Introduction

‘Ferroptosis’ is a type of iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy. It is driven by cellular metabolism and iron-dependent lipid peroxidation. The main mechanism of ferroptosis is to catalyze the highly expressed unsaturated fatty acids on cell membranes under the action of divalent ferrous iron or lipoxygenase, which results in lipid peroxidation and induces cell death [1]. High expression of P53RRA can promote ferroptosis in lung cancer cells [4], and License 4.0 (CC BY). Whether ferroptosis-related genes are related to the prognosis of NSCLC patients is not known. Differential analysis was undertaken to screen ferroptosis-related genes associated with cancer prognosis. A prognostic model was constructed based on ferroptosis-related genes to predict the survival of patients. Functional enrichment analysis of differentially expressed genes (DEGs) in low-risk and high-risk groups was conducted, and correlations between enriched pathways and immune status were studied

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