Abstract
BACKGROUND: Iron metabolism related genes participate in cell proliferation, cell growth, and redox cycling in multiple cancers. Limited studies have revealed the roles and clinical significance of iron metabolism in the pathogenesis and prognosis of lung cancer. METHODS: A total of 119 iron metabolism related genes were extracted from MSigDB database and their prognostic values were determined in The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) dataset and the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. Immunohistochemistry technique and correlations with immune cell infiltration, gene mutation and drug resistance were used to identify the potential and underlying mechanisms of STEAP1 and STEAP2 as prognostic biomarkers of LUAD. RESULTS: The expression of STEAP1 and STEAP2 are negatively associated with the prognosis of LUAD patients both at the mRNA and protein level. The expression of STEAP1 and STEAP2 was not only negatively correlated with the trafficking degree of CD4+ T immune cells and positively related to most immune cells' trafficking degree, but also significantly associated with gene mutation status, particularly with mutations on TP53 and STK11. Four types of drug resistance showed significant correlation with the expression level of STEAP1 while 13 types of drug resistance were associated with the expression level of STEAP2. CONCLUSION: Multiple iron metabolism related genes including STEAP1 and STEAP2 are significantly associated with the prognosis of LUAD patients. STEAP1 and STEAP2 might affect the prognosis of LUAD patients partially through immune cell infiltration, gene mutation and drug resistance, which indicated they were independent prognostic factors for LUAD patients.