Construction Of A Prognostic Model Of Ferroptosis-related Genes In Lung Adenocarcinoma

Objective: Lung cancer is a malignant tumor that threatens human health worldwide,with lung adenocarcinoma(LUAD)being the most common histological type.Ferroptosis is a newly discovered type of regulated cell death,and recent evidence suggests that inducing ferroptosis in tumor cells has potential to be a cancer treatment.Studies have shown that ferroptosis-related gene expression is associated with patient prognosis in a variety of tumors.This study aimed to establish prognostic genes associated with ferroptosis to predict the prognosis of lung adenocarcinoma patients and to explore the association and potential mechanism between ferroptosis and lung adenocarcinoma.Methods: The lung adenocarcinoma patient dataset was collected from The Cancer Genome Atlas(TCGA)database and ferroptosis-related genes were obtained from Ferr Db database to identify ferroptosis-related genes.Univariate Cox regression analyses were performed to identify prognostic genes.Prognostic genes were intersected with ferroptosis-related genes to determine prognostic ferroptosis-related genes.The prognostic model was generated from LASSO Cox regression analysis.Patients were divided into high-risk subgroups and low-risk subgroups.The prognostic genes was verified by Univariate and multivariate Cox regression analysis,Kaplan-meier survival curve and ROC curve analysis.GO enrichment and KEGG enrichment analyses explored differentially expressed genes’ functional roles between high-risk and low-risk subgroups.Ss GSEA analysis was used to better understand the characteristics and functions of immune cells and immune function in different subgroups.Results: 45 differentially expressed ferroptosis-related genes were obtained.Six prognostic ferroptosis-related genes(ACSL4,ALOX15,CISD1,FANCD2,PHKG2 and PEBP1)were identified by the intersection of ferroptosis-related genes and prognostic genes.PHKG2,CISD1 and FANCD2 genes were highly expressed in lung adenocarcinoma tissues,while ACSL4,ALOX15 and PEBP1 genes were low expressed in lung adenocarcinoma tissues.A prognostic model composed was established by LASSO Cox regression.Patients were divided into two subgroups,high risk and low risk.The proportion of patients with a high TNM stage in the high-risk subgroup was higher than that in the low-risk subgroup.In comparison with patients in the low-risk group,those in the high-risk group had lower survival rates and showed a significantly poor overall survival and progression-free survival.The prognostic model was an independent prognostic factor for overall survival and progression-free survival.The model had good prognostic ability in 1,3 and 5 years.Enrichment analysis showed that the differential genes in the high and low risk groups were mainly involved in the biological processes related to cell division.Scores of immune cells and immune pathways showed significant changes in immune status in the high-risk group.Conclusions: In this study,six ferroptosis-related genes associated with survival were identified by bioinformatics methods.The prognostic model based on these six genes could distinguish high-risk and low-risk populations.The model is an independent predictor of prognosis of lung adenocarcinoma and has high specificity and sensitivity in predicting overall survival and progression-free survival.ferroptosis provides a new reference and research direction for prognosis assessment and targeted therapy of lung adenocarcinoma.