Research Paper Volume 13, Issue 16 pp 20438—20467

Ceruloplasmin correlates with immune infiltration and serves as a prognostic biomarker in breast cancer

Fei Chen1, *, , Bihui Han1, *, , Yanxiu Meng1, *, , Yu Han1, , Bing Liu1, , Bo Zhang1, , Yanzhong Chang1, , Pengxiu Cao1, , Yumei Fan1, , Ke Tan1, ,

  • 1 Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, Hebei, China
* Equal contribution

Received: January 30, 2021       Accepted: August 2, 2021       Published: August 19, 2021
How to Cite

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-invasive carcinoma (BRCA) is the most frequent and malignant tumor in females. Ceruloplasmin (CP) is a multifunctional molecule involved in iron metabolism, but its expression profile, prognostic potential and relationship with immune cell infiltration in BRCA are unknown. Ceruloplasmin mRNA and protein expression was significantly decreased in BRCA patients according to the Oncomine, UALCAN, GEPIA and TCGA databases. Ceruloplasmin expression was strongly correlated with various clinicopathological features of BRCA patients. BRCA patients with high ceruloplasmin expression exhibited shorter survival times than those with low ceruloplasmin expression based on the Kaplan-Meier plotter and PrognoScan databases. GO and KEGG analyses and GSEA revealed a strong correlation between ceruloplasmin and various immune-related pathways. Ceruloplasmin expression was significantly associated with the infiltration of immune cells into tumor sites by analyzing the TIMER and CIBERSORT. Additionally, ceruloplasmin was positively correlated with immune checkpoints in BRCA. These findings suggest that low ceruloplasmin expression correlates with a favorable prognosis and tumor immune cell infiltration in BRCA patients. Ceruloplasmin may serve as a therapeutic target and predict the efficacy of immunotherapy for BRCA.


ACC: adrenocortical carcinoma; AUC: area under the curve; AOM: azoxymethane; BRCA: breast-invasive carcinoma; BP: biological process; CP: ceruloplasmin; CNS: central nervous system; CC: cell component; DSS: disease-specific survival; EMT: epithelial-mesenchymal transition; FPS: first progression; GO: gene ontology; GSEA: gene set enrichment analysis; GPI: glycosylphosphatidylinositol; HPA: Human Protein Atlas; KEGG: Kyoto Encyclopedia of Genes and Genomes; MF: molecular function; NPI: Nottingham Prognostic Index; OS: overall survival; PPS: postprogression survival; PPI: protein-protein interaction; RFS: recurrence-free survival; ROC: receiver operating characteristic; RCC: renal cell carcinoma; SBR: Scarff-Bloom-Richardson; TCGA: The Cancer Genome Atlas; TNBC: non-basal-like and non-triple-negative breast cancer; TME: tumor microenvironment.