Abstract
PURPOSE: Cytochrome b561 (CYB561) is a transmembrane protein and participates in ascorbate recycling and iron homeostasis. However, its role in breast cancer remains unclear. PATIENTS AND METHODS: In this study, we explored the expression pattern and prognostic value of CYB561 in breast cancer through The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), PrognoScan and Kaplan-Meier Plotter and confirmed its mRNA expression in human breast cell lines. LinkedOmics, Metascape and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were applied to investigate the co-expression genes and construct microRNA (miRNA) networks associated with CYB561. The correlations between CYB561 and immune infiltration cells and genes were also illustrated. RESULTS: The CYB561 expression was upregulated in breast cancer tissues and cell lines and significantly correlated with the clinical features of breast cancer patients. High CYB561 expression was associated with poor survival and was an independent risk factor for overall and disease-specific survival. Functional enrichment analysis showed that CYB561 and its co-expressed genes were mainly enriched in lipid biosynthetic process, Wnt signaling pathway, Hippo signaling pathway, etc. The miRNA network analysis suggested that hsa-miR-497 was negatively correlated with CYB561 expression and was predicted to direct target CYB561. CYB561 expression was positively correlated with infiltrating levels of CD4+ T cells, neutrophils and dendritic cells in breast cancer. Subsequent analysis found that B cells could predict the outcome of breast cancer. Also, CYB561 showed strong correlations with diverse immune marker sets in breast cancer. CONCLUSION: CYB561 may serve as a potential prognostic biomarker and target for breast cancer. Our findings laid foundation for future research on molecular mechanisms of CYB561 in breast cancer.