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Published on: February 4, 2021
Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients
Li Ma1, Lisha Qi2, Shuangjing Li3
1Department of Neuro-Oncology and Neurosurgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Background:
Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy.
Methods:
Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses.
Results:
HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis.
Conclusions:
Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine.
Key Points:
Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.
Insights
Histone deacetylase 3 (HDAC3) plays a critical role in breast cancer brain metastasis. Targeting cytoplasmic HDAC3 may offer a new therapeutic strategy for improving patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Brain metastasis is a significant challenge in breast cancer treatment with poor outcomes.
- While pan-histone deacetylase (HDAC) inhibitors show promise, the specific HDAC involved in brain metastasis remains unclear.
Purpose of the Study:
- To identify specific histone deacetylase (HDAC) proteins correlated with breast cancer brain metastasis.
- To explore HDAC3 as a potential therapeutic target for precision cancer therapy.
Main Methods:
- Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 breast invasive ductal carcinoma samples.
- Kaplan-Meier curves and Cox regression analyses to evaluate survival outcomes.
Main Results:
- HDAC1, HDAC2, and cytoplasmic HDAC3 were independent prognostic factors for overall survival.
- Cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival.
- Cytoplasmic HDAC3 expression was upregulated in brain metastases, while nuclear expression was downregulated.
Conclusions:
- HDAC3 plays a critical role in breast cancer brain metastasis.
- Cytoplasmic HDAC3 is a promising therapeutic target for precision medicine in breast cancer.
