Abstract
Breast cancer (BC) is the most common malignancy with high morbidity and mortality in females worldwide. Emerging evidence indicates that transferrin receptor 1 (TfR1) plays vital roles in regulating cellular iron import. However, the distinct role of TfR1 in BC remains elusive. TfR1 expression was investigated using the TCGA, GEO, TIMER, UALCAN and Oncomine databases. The prognostic potential of TfR1 was evaluated by Kaplan-Meier (KM) plotter and univariate and multivariate Cox regression analyses. Moreover, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) were used to explore the molecular mechanism of TfR1. The potential link between TfR1 expression and infiltrating abundances of immune cells was examined through the TIMER and CIBERSORT algorithm. The expression of TfR1 was dramatically upregulated in BC tissues. Increased TfR1 expression and decreased methylation levels of TfR1 were strongly correlated with multiple clinicopathological parameters. Elevated TfR1 expression was associated with a poor survival rate in BC patients. The nomogram model further confirmed that TfR1 could act as an independent prognostic biomarker in BC. The results of GO, KEGG and GSEA revealed that TfR1 was closely correlated with multiple signaling pathways and immune responses. Additionally, TfR1 was positively associated with the infiltration abundances of six major immune cells, including CD4+ T cells, CD8+ T cells, B cells, neutrophils, macrophages, and dendritic cells in BC. Interestingly, TfR1 influenced prognosis partially through immune infiltration. These comprehensive bioinformatics analyses suggest that TfR1 is a new independent prognostic biomarker and a potential target for immunotherapy in BC.
Highlights
Among malignancies, breast cancer (BC) is the leading cause of cancer death and has the highest morbidity rate in women worldwide [1]
Upregulated transferrin receptor 1 (TfR1) expression was observed in BLCA, CHOL, COAD, ESCA, HNSC, KICH, LUSC, LIHC, STAD and UCEC tissues, whereas downregulated TfR1 expression was observed in LUAD, KIRP, KIRC, PRAD and THCA tissues (Figure 1A)
TfR1 expression was further investigated through the TCGA database, and we found that TfR1 expression was markedly upregulated in BC tissues (Figure 1E)
Summary
Breast cancer (BC) is the leading cause of cancer death and has the highest morbidity rate in women worldwide [1]. With the development of treatment, the survival rate of BC patients has been significantly improved [2, 3]. A large number of patients still die from BC because of metastasis and/or chemoradiotherapeutic resistance [2,3,4]. It is crucial to investigate the mechanisms that lead to the incidence of BC metastasis and chemoresistance and identify some prognosis-related factors of BC. Most cancer cells need a relatively high concentration of cellular iron to ensure their rapid proliferation and growth [7, 8]. Alterations in the expression of iron homeostasis-associated genes have been identified as potential prognostic biomarkers or therapeutic targets in some cancers [9, 10]
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