Abstract
Background: Lung adenocarcinoma (LUAD) is a malignant tumor with high heterogeneity and poor prognosis. Ferroptosis, a form of regulated cell-death–related iron, has been proven to trigger inflammation-associated immunosuppression in the tumor microenvironment, which promotes tumor growth. Therefore, the clinical prognostic value of ferroptosis-related genes in LUAD needs to be further explored.Method: In this study, we downloaded the mRNA expression profiles and corresponding clinical data of LUAD patients from the Cancer Genome Atlas database. The least absolute shrinkage and selection operator (LASSO) Cox regression model was utilized to construct ferroptosis-related gene signature. Based on these, we established the nomograms for prognosis prediction and validated the model in the GSE72094 dataset. The cell type was identified using the CIBERSORT algorithm for estimating relative subsets of RNA transcripts, which was then used to screen significant tumor immune-infiltrating cells associated with the LUAD prognosis prediction model. Subsequently, we applied co-expression analysis to reveal the relationship between ferroptosis-related genes and significant immune cells.Results: The univariate COX regression analysis showed that 20 genes were associated with the overall survival (OS) as prognostic differentially expressed genes (DEGs) (FDR <0.05). Patients were divided into two risk groups using a 13-gene signature, with the high-risk group having a significantly worse OS than their low-risk counterparts (p < 0.001). We used receiver operating characteristic (ROC) curve analysis to confirm the predictive capacity of the signature. Besides, we identified seven pairs of ferroptosis-related genes and tumor-infiltrating immune cells associated with the prognosis of LUAD patients.Conclusion: In this study, we construct a ferroptosis-related gene signature that can be used for prognostic prediction in LUAD. In addition, we reveal a potential connection between ferroptosis and tumor-infiltrating immune cells.
Highlights
Lung cancer is the most common malignant tumor in the world and has become the leading cause of death among other cancers
Data that contained RNA expression profiles and relevant clinical information of 535 lung adenocarcinoma patients were downloaded from the Cancer Genome Atlas (TCGA) database
There were 71 ferroptosis-related genes that were differentially expressed between tumor tissues and adjacent nontumorous tissues
Summary
Lung cancer is the most common malignant tumor in the world and has become the leading cause of death among other cancers. There would be 2.2 million new cases of lung cancer and 1.8 million deaths worldwide in 2020, making lung cancer rank first in terms of incidence and mortality of malignant tumors (Siegel et al, 2021). Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of all lung cancer patients (Ettinger et al, 2017). Lung adenocarcinoma (LUAD) is a major histologic type of NSCLC, accounting for approximately 50% of all cases (Travis et al, 2015). Considering the poor prognosis of LUAD patients, it is imperative to develop a novel prognostic model. Lung adenocarcinoma (LUAD) is a malignant tumor with high heterogeneity and poor prognosis. The clinical prognostic value of ferroptosis-related genes in LUAD needs to be further explored
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