CYB561 is a potential therapeutic target for breast cancer and is associated with immune cell infiltration

Eur J Med Res. 2024 Aug 12;29(1):414. doi: 10.1186/s40001-024-02010-3.

Abstract

Background: Breast cancer (BC), a common malignant tumor originating from the terminal ductal lobular unit of the breast, poses a substantial health risk to women. Previous studies have associated cytochrome b561 (CYB561) with a poor prognosis in BC; however, its underlying mechanism of this association remains unclear.

Methods: We investigated the expression of CYB561 mRNA in BC using databases such as The Cancer Genome Atlas, Gene Expression Omnibus, Tumor-Normal-Metastatic plot, and Kaplan-Meier plotter databases. The prognostic value of CYB561 protein in BC was assessed in relation to its expression levels in tumor tissue samples from 158 patients with BC. The effect of CYB561 on BC progression was confirmed using in vivo and in vitro experiments. The biological functions and related signaling pathways of CYB561 in BC were explored using gene microarray, Innovative Pathway, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The correlation between CYB561 and the BC tumor immune microenvironment was evaluated using the CIBERSORT algorithm and single-cell analysis and further validated through immunohistochemistry of serial sections.

Results: Our study demonstrated that upregulation of CYB561 expression predicted poor prognosis in patients with BC and that CYB561 knockdown inhibited the proliferation, migration, and invasive ability of BC cells in vitro. CYB561 knockdown inhibited BC tumor formation in vivo.CYB561 was observed to modulate downstream tropomyosin 1 expression. Furthermore, CYB561 expression was associated with macrophage M2 polarization in the BC immune microenvironment.

Conclusions: Elevated CYB561 expression suggests a poor prognosis for patients with BC and is associated with macrophage M2 polarization in the BC microenvironment. Therefore, CYB561 could potentially serve as a therapeutic target for BC treatment.

Keywords: Bioinformatics; Breast cancer (BC); Cytochrome b561 (CYB561); Immune infiltration; Prognosis; Single-cell sequence.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Prognosis
  • Tumor Microenvironment* / immunology

Substances

  • Biomarkers, Tumor
  • Membrane Proteins