Abstract
CD24 is associated with unfavourable prognoses in various cancers, but the prevalence of CD24 expression and its influence on clinical outcome in subtypes of breast cancers remain unclear. CD24 expression was analyzed by immunohistochemistry in 747 breast cancer tissues, and DNA methylation and histone modification status in the promoter region of CD24 were assessed using bisulfite sequencing and chromatin immunoprecipitation assay. 213 (28.5%) samples exhibited high CD24 expression in the membrane and/or cytoplasm of breast cancer cells, and CD24 overexpression was significantly correlated with the presence of lymph node metastasis and more advanced pathological stage. Patients with CD24-high tumours had significantly shorter patient survival than those with CD24-low tumours. Importantly, multivariate analysis that included tumour size, lymph node metastasis and chemotherapy demonstrated that high CD24 expression is independently associated with poorer survival in luminal A and triple-negative breast cancer (TNBC) subtypes. Furthermore, CD24 gene expression was associated with histone acetylation independent of DNA methylation, suggesting its epigenetic regulation in breast cancer. Our results suggest that CD24 overexpression is an independent unfavourable prognostic factor in breast cancer, especially for luminal A and TNBC subtypes, and CD24 may be a promising therapeutic target for specific subtypes of breast cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Biomarkers, Tumor / genetics
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CD24 Antigen / genetics*
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Cell Line, Tumor
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DNA Methylation / genetics
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Epigenesis, Genetic / genetics
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Female
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Humans
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Immunohistochemistry / methods
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Lymphatic Metastasis / genetics
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Lymphatic Metastasis / pathology
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Middle Aged
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Prognosis
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Receptor, ErbB-2 / genetics
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Triple Negative Breast Neoplasms / genetics*
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Triple Negative Breast Neoplasms / pathology*
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Young Adult
Substances
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Biomarkers, Tumor
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CD24 Antigen
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CD24 protein, human
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Receptor, ErbB-2
Grants and funding
This work was supported by the Kyungpook National University Research Fund, 2013 & 2014 (MJK), a grant (SMX1132711 [YLC]) from the Samsung Biomedical Research Institute, the R&D program for Society of the National Research Foundation (NRF) (2013M3C8A1079312 [YKS]) and Basic Science Research Program through the NRF (NRF-2012R1A1A3014050 [YLC]) funded by the Ministry of Science, ICT & Future Planning. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Two authors (JH and KS) are employed by a commercial company, Gencurix for JH and ABION for KS, respectively. These commercial affiliations provided support in the form of salaries for authors [JH and KS], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.