Abstract
Breast cancer (BC) affects the breast tissue and is the second most common cause of mortalities among women. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS). We constructed a prognostic multigene signature based on ferroptosis-associated differentially expressed genes (DEGs). Moreover, we comprehensively analyzed the role of ferroptosis-associated miRNAs, lncRNAs, and immune responses. A total of 259 ferroptosis-related genes were extracted. KEGG function analysis of these genes revealed that they were mainly enriched in the HIF-1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, and PPAR signaling pathway. Fifteen differentially expressed genes (ALOX15, ALOX15B, ANO6, BRD4, CISD1, DRD5, FLT3, G6PD, IFNG, NGB, NOS2, PROM2, SLC1A4, SLC38A1, and TP63) were selected as independent prognostic factors for BC patients. Moreover, T cell functions, including the CCR score, immune checkpoint, cytolytic activity, HLA, inflammation promotion, para-inflammation, T cell co-stimulation, T cell co-inhibition, and type II INF responses were significantly different between the low-risk and high-risk groups of the TCGA cohort. Immune checkpoints between the two groups revealed that the expressions of PDCD-1 (PD-1), CTLA4, LAG3, TNFSF4/14, TNFRSF4/8/9/14/18/25, and IDO1/2 among others were significantly different. A total of 1185 ferroptosis-related lncRNAs and 219 ferroptosis-related miRNAs were also included in this study. From the online database, we identified novel ferroptosis-related biomarkers for breast cancer prognosis. The findings of this study provide new insights into the development of new reliable and accurate cancer treatment options.
Highlights
Breast cancer (BC) affects the breast tissue and metastasizes to the bones and lungs
Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS), which is distinct from apoptosis
Enrichment analysis of ferroptosis-related genes BP of target genes were enriched in response to oxidative stress, multicellular organismal homeostasis, cofactor metabolic processes, and response to metal ion activities among others; MF were mainly enriched in ferric iron binding, aldo-keto reductase (NADP) activity, and oxidoreductase activity among others; CC were mainly enriched in the regulation of epithelial cell proliferation, lipid droplet, apical plasma membrane, and astrocyte projection among others; Kyoto Encyclopedia of Genes and Genomes (KEGG) were mainly enriched in ferroptosis, hypoxia-inducible factor (HIF)−1 signaling pathway, NOD-like receptor signaling pathway, central carbon metabolism in cancer, Kaposi sarcoma-associated herpesvirus infection, and PPAR signaling pathway (Fig. 1)
Summary
Breast cancer (BC) affects the breast tissue and metastasizes to the bones and lungs. BC has very high incidence rates[1]. It is the second most common cause of mortalities among women[2], accounting for an estimated 24% of diagnosed cases and 15% of mortality cases among them[3]. Due to the asymptomatic early stages, BC is often diagnosed in the advanced stages, leading to serious outcomes. Diagnosis and Studies on ferroptosis in tumors are on the ascendancy. Ferroptosis is an iron-dependent cell death mode that is characterized by intracellular accumulation of reactive oxygen species (ROS), which is distinct from apoptosis
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