Abstract
Purpose
The expression of cytochrome B561 (CYB561) and its role in breast cancer (BC) prognosis remain unclear. We analyzed the differential expression and prognostic value of CYB561 using online databases and a clinical cohort through bioinformatics and immunohistochemistry.
Methods
The differential expression of CYB561 and its association with BC were analyzed using the tumor immune estimation resource (TIMER), gene expression profiling interaction analysis2 (GEPIA2), Human Protein Atlas, Cancer Cell Line Encyclopedia, and Kaplan–Meier Plotter website. Important pathways of CYB561 enrichment were explored using gene set enrichment analysis. Immunohistochemistry detected CYB561 expression in normal breast, breast hyperplasia, ductal carcinoma in situ (DCIS), para-cancer, and invasive BC groups. Association between CYB561 expression and BC prognosis was analyzed using Kaplan–Meier and Cox regression analyses.
Results
CYB561 mRNA expression was higher in GEPIA and TIMER BC patients than in para-cancer tissues. CYB561 was expressed in the glandular epithelium and myoepithelium, with positive localization in the cytoplasm and cell membrane. CYB561 protein expression significantly differed among the groups. CYB561 expression was correlated with ERBB2/HER2 and infiltrating CD4+ T cells in GEPIA and TIMER BC patients and associated with HER2 status, histological grade, and molecular subtypes in the clinical cohort but not related to tumor-infiltrating lymphocytes. CYB561 mRNA overexpression predicted reduced recurrence-free survival and overall survival in BC. Patients with CYB561 expression had significantly reduced overall survival and increased risk of death.
Conclusion
CYB561 can serve as an effective clinical prognostic biomarker for BC.
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Data availability
Three public datasets were obtained from TIMER (https://cistrome.ShinYapps.io/timer/), GEPIA 2(http://gepia2.cancer-pkucn/), and Kaplan–Meier Plotter websites (https://kmplot.com/analysis/).
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Acknowledgements
We would like to thank Project of Basic Research for application of Science and Technology Department of Qinghai Province for its funding support and Editage (www.editage.cn) for English language editing.
Funding
This work was supported by Project of Basic Research for application of Science and Technology Department of Qinghai Province (2019-ZJ-7003).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [XZ], [GS], [DR], [XG], [JH] and [JZ]. The first draft of the manuscript was written by [XZ] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Zhou, X., Shen, G., Ren, D. et al. Expression and clinical prognostic value of CYB561 in breast cancer. J Cancer Res Clin Oncol 148, 1879–1892 (2022). https://doi.org/10.1007/s00432-022-03928-z
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DOI: https://doi.org/10.1007/s00432-022-03928-z