Dataset Information

Establishment of a ferroptosis-related gene signature for prognosis in lung adenocarcinoma patients.

ABSTRACT:

Objective

Lung cancer is the most common malignancy worldwide and exhibits both high morbidity and mortality. In recent years, scientists have made substantial breakthroughs in the early diagnosis and treatment of lung adenocarcinoma (LUAD), however, patient prognosis still shows vast individual differences. In this study, bioinformatics methods were used to identify and analyze ferroptosis-related genes to establish an effective signature for predicting prognosis in LUAD patients.

Methods

The gene expression profiles of LUAD patients with complete clinical and follow-up information were downloaded from two public databases, univariate Cox regression and multivariate Cox regression analysis were used to obtain ferroptosis-related genes for constructing the prognos tic risk model, AUC and calibration plot were used to evaluate the predictive accuracy of the FRGS and nomogram.

Results

A total of 74 ferroptosis-related differentially expressed genes (DEGs) were identi fied between LUAD and normal tissues from The Cancer Genome Atlas (TCGA) database. A five-gene panel for prediction of LUAD prognosis was established by multivariate regression and was verified using the GSE68465 cohort from the Gene Expression Omnibus (GEO) database. Patients were divided into two different risk groups according to the median risk score of the five genes. Based on Kaplan-Meier (KM) analysi, the OS rate of the high-risk group was markedly worse than that of the low-risk group. We also found that risk score was an independent prognostic indicator. The receiver operating characteristic ROC curve showed that the proposed model had good prediction ability. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses indicated that risk score was prominently enriched in ferroptosis processes. Moreover, at the score of immune-associated gene sets, significant differences were found between the two risk groups.

Conclusions

This study demonstrated that ferroptosis-related gene signatures can be used as a potential predictor for the prognosis of LUAD, thus providing a novel strategy for individualized treatment in LUAD patients.

SUBMITTER: Cai J

PROVIDER: S-EPMC8351575 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFerroptosis is a recently recognized non-apoptotic cell death that is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in esophageal adenocarcinoma (EAC) remains unclear. This study aims to explore the ferroptosis-related genes (FRG) expression profiles and their prognostic values in EAC.MethodsThe FRG data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate cox regressions were used to identify the prognostic FRG, and the predictive ROC model was established using the independent risk factors. GO and KEGG enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and TIMER database. Finally, SDG were verified in clinical EAC specimens and normal esophageal mucosal tissues.ResultsTwenty-eight significantly different FRG were screened from 78 EAC and 9 normal tissues. Enrichment analyses showed these SDG were mainly related to the iron-related pathways and metabolisms of ferroptosis. Gene network demonstrated the TP53, G6PD, NFE2L2 and PTGS2 were the hub genes in the biology of ferroptosis. Cox regression analyses demonstrated four FRG (CARS1, GCLM, GLS2 and EMC2) had prognostic values for overall survival (OS) (all P < 0.05). ROC curve showed better predictive ability using the risk score (AUC = 0.744). Immune cell enrichment analysis demonstrated that the types of immune cells and their expression levels in the high-risk group were significant different with those in the low-risk group (all P < 0.05). The experimental results confirmed the ALOX5, NOX1 were upregulated and the MT1G was downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05).ConclusionsWe identified differently expressed ferroptosis-related genes that may involve in EAC. These genes have significant values in predicting the patients' OS and targeting ferroptosis may be an alternative for therapy. Further studies are necessary to verify these results of our study.

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