Abstract
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.
Highlights
Breast-invasive carcinoma (BRCA) is the most frequent malignant tumor in females worldwide [1]
The expression of ceruloplasmin was obviously decreased in BRCA, cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), kidney chromophobe (KICH), kidney renal papillary cell carcinoma (KIRP), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), rectum adenocarcinoma (READ) and thyroid carcinoma (THCA) tissues compared with normal tissues and was increased in cancer versus normal tissues in the kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), stomach adenocarcinoma (STAD) and uterine corpus endometrial carcinoma (UCEC) tissues (Figure 1A)
We found that ceruloplasmin mRNA and protein expression was remarkably downregulated and correlated with sex, race, tumor clinical stage and pathological grade (Figures 1–4)
Summary
Breast-invasive carcinoma (BRCA) is the most frequent malignant tumor in females worldwide [1]. Other treatment strategies include chemotherapy, radiotherapy, endocrine agents and immunotherapy. These treatments have reduced the morbidity and mortality of BRCA patients, the prognosis of BRCA remains poor [2, 3]. Ceruloplasmin (CP), a multicopper oxidase, is a mammalian plasma ferroxidase [5]. The GPI-anchored form of ceruloplasmin is ubiquitously expressed in various tissues and cells, including hepatocytes, macrophages, astrocytes, leptomeningeal cells and Sertoli cells [12,13,14]. Multiple activities and physiological roles of ceruloplasmin have been identified, including ferroxidase and antioxidant activity and the mediation of iron homeostasis, transportation of copper, and oxidation of organic amines [5]. Ceruloplasmin is recognized as an acute-phase protein activated under different conditions, such as infection, inflammation, diabetes and trauma [15]
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