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

Abstract

Zeyu Zhang,1 Xiangyuan Qiu,1 Yuanliang Yan,2 Qiujiu Liang,2 Yuan Cai,3 Bi Peng,3 Zhijie Xu,3,4 Fada Xia1 1Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Pathology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Zhijie XuDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaEmail [email protected] XiaDepartment of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaEmail [email protected]: 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 associated 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.Keywords: breast cancer, AKR1C1, ferroptosis, immune microenvironment, immune infiltration

Keywords

• breast cancer
• akr1c1
• ferroptosis
• immune microenvironment
• immune infiltration