Evaluation of Ferroptosis-related Gene AKR1C1 as a Novel Biomarker Associated with the Immune Microenvironment and Prognosis in Breast Cancer

Background: Ferroptosis is the latest-discovered, iron-dependent form of regulated cell death. It has been increasingly recognized that ferroptosis-related genes participate in oncogenesis and development of cancers, including breast cancer (BRCA). Thus, It is important to explore the biofunctions of ferroptosis-related genes in BRCA. Methods: Transcriptome microarray datasets (GSE22358, GSE9014 and GSE8977, GSE2990 and GSE2034) and TCGA-BRCA were retrieved for analyses. And a variety of computational tools were used to identify the roles and associated biological functions in BRCA. Results: Two ferroptosis-related genes (AKR1C1 and AKR1C3) were significantly expressed in GSE22358, GSE9014 and GSE8977. Higher expression of AKR1C1 was related with favorable prognosis. TCGA-BRCA further confirmed the expression of AKR1C1 and the prognostic value of AKR1C1. Co-expression analyses showed the most enriched GO term and KEGG pathways were termination of DNA-templated transcription and Fanconi anemia pathway. Subsequently, immunological analyses showed AKR1C1 was significantly asso-ciated with various immune infiltration cells; among these, dendritic cells, neutrophils, macrophages were the top three infiltrating cells. Furthermore, AKR1C1 was also associated with multiple immunostimulatory molecules and chemokines, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, IL-6, BTLA, CXCL2, and CCR7. These results indicated the potential roles of AKR1C1 in the immune reaction during the pathogenesis of breast cancer. Conclusion: This study firstly demonstrated that ferroptosis-related gene, AKR1C1, could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.