European Journal of Medical Research (Aug 2024)

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

  • Jian Zhuo,
  • Yanchun Zhao,
  • Ruiying Hao,
  • He Li,
  • Zilin Zheng,
  • Luxian Dai,
  • Ankang Sheng,
  • Hanyu Yao,
  • Yubao Tang,
  • Rao Wang,
  • Xiaohong Yang,
  • Weiguang Liu

DOI
https://doi.org/10.1186/s40001-024-02010-3
Journal volume & issue
Vol. 29, no. 1
pp. 1 – 18

Abstract

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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.

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