Screening and biomarker assessment of ferroptosis genes FLT3 and ALOX5 in lung adenocarcinoma

Abstract Objectives Ferroptosis is a unique process of cell death that specifically requires iron. We investigated ferroptosis genes and their function in lung adenocarcinoma (LUAD) patients. Methods Data on the expression levels of genes associated with ferroptosis were collected from the FerrDb and the Cancer Genome Atlas database. Kaplan-Meier Plotter was employed to generate the survival curves of LUAD patients with high vs low expression of ferroptosis genes. The relationship between immune cell infiltration and ferroptosis genes was analyzed via TIMMER. Immunohistochemical staining was employed to quantitatively evaluate gene expression in 43 LUAD patients. Results A total of 89 ferroptosis genes were found to have significant differential expression between LUAD and normal tissues (p<0.05), 23 of which were selected and consistent prognostic trends were observed based on analysis of RNA-Seq and RNA microarray data (p<0.05). These 23 ferroptosis genes were assigned to 10 high-abundance pathways and 18 functional categories. Besides, the expression of ALOX5 and FTL3 demonstrated a positive correlation with sets of immune markers. The expression of ALOX5 exhibited a positive correlation with the levels of infiltration of dendritic cells, macrophages, neutrophils, and CD4+ T cells, while FLT3 expression correlated with the infiltration of B cells, CD4+ T cells, neutrophils, and dendritic cells. Furthermore, ALOX5 was confirmed to be downregulated in lung tumor tissues (p<0.01). Conclusions Our findings show that the ferroptosis genes FLT3 and ALOX5 play prominent roles in immune cell infiltration during LUAD progression and may serve as prognostic biomarkers for LUAD.