Research Paper Volume 13, Issue 17 pp 21671—21699
Integrated analysis identifies TfR1 as a prognostic biomarker which correlates with immune infiltration in breast cancer
- 1 Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei 050024, China
Received: March 4, 2021 Accepted: August 24, 2021 Published: September 13, 2021https://doi.org/10.18632/aging.203512
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Copyright: © 2021 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.