ArticleBMC cancer2018
Tumoral BRD4 expression in lymph node-negative breast cancer: association with T-bet+ tumor-infiltrating lymphocytes and disease-free survival.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting BRD4 in gastric cancer: promoting apoptosis and suppressing tumor progression.Frontiers in pharmacology · 2026Article
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Apabetalone (RVX-208): A Potential Epigenetic Therapy for the Treatment of Cardiovascular, Renal, Neurological, Viral, and Cancer Disorders.ACS pharmacology & translational science · 2024Review
- Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review.Frontiers in immunology · 2024Review
- Loss of BRD4 induces cell senescence in HSC/HPCs by deregulating histone H3 clipping.EMBO reports · 2023Article
- Acute respiratory distress syndrome enhances tumor metastasis into lungs: Role of BRD4 in the tumor microenvironment.International immunopharmacology · 2023Article
- It Runs in the Bromodomain Family: Speckled Proteins (SP) Play a Role in the Antitumor Immune Response in Solid Tumors.International journal of molecular sciences · 2022Article
- The BET family in immunity and disease.Signal transduction and targeted therapy · 2021Review
- Immunotyping of tumor-infiltrating lymphocytes in triple-negative breast cancer and genetic characterization.Oncology letters · 2020Article
- The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology.Life (Basel, Switzerland) · 2020Article
- Fifteen mRNA-lncRNA expression-based signature predicted the survival of late-staged head and neck squamous cell carcinoma.Bioscience reports · 2020Article
- SIRT7 Is a Prognostic Biomarker Associated With Immune Infiltration in Luminal Breast Cancer.Frontiers in oncology · 2020Article
- T-betBreast cancer research and treatment · 2019Article
- Therapeutic Targeting of BRD4 in Head Neck Squamous Cell Carcinoma.Theranostics · 2019Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundWe previously observed that T-bet+ tumor-infiltrating T lymphocytes (T-bet+ TILs) in primary breast tumors were associated with adverse clinicopathological features, yet favorable clinical outcome. We identified BRD4 (Bromodomain-Containing Protein 4), a member of the Bromodomain and Extra Terminal domain (BET) family, as a gene that distinguished T-bet+/high and T-bet-/low tumors. In clinical studies, BET inhibitors have been shown to suppress inflammation in various cancers, suggesting a potential link between BRD4 and immune infiltration in cancer. Hence, we examined the BRD4 expression and clinicopathological features of breast cancer.
methodsThe cohort consisted of a prospectively ascertained consecutive series of women with axillary node-negative breast cancer with long follow-up. Gene expression microarray data were used to detect mRNAs differentially expressed between T-bet+/high (n = 6) and T-bet-/low (n = 41) tumors. Tissue microarrays (TMAs) constructed from tumors of 612 women were used to quantify expression of BRD4 by immunohistochemistry, which was analyzed for its association with T-bet+ TILs, Jagged1, clinicopathological features, and disease-free survival.
resultsMicroarray analysis indicated that BRD4 mRNA expression was up to 44-fold higher in T-bet+/high tumors compared to T-bet-/low tumors (p = 5.38E-05). Immunohistochemical expression of BRD4 in cancer cells was also shown to be associated with T-bet+ TILs (p = 0.0415) as well as with Jagged1 mRNA and protein expression (p = 0.0171, 0.0010 respectively). BRD4 expression correlated with larger tumor size (p = 0.0049), pre-menopausal status (p = 0.0018), and high Ki-67 proliferative index (p = 0.0009). Women with high tumoral BRD4 expression in the absence of T-bet+ TILs exhibited a significantly poorer outcome (log rank test p = 0.0165) relative to other subgroups.
conclusionsThe association of BRD4 expression with T-bet+ TILs, and T-bet+ TIL-dependent disease-free survival suggests a potential link between BRD4-mediated tumor development and tumor immune surveillance, possibly through BRD4's regulation of Jagged1 signaling pathways. Further understanding BRD4's role in different immune contexts may help to identify an appropriate subset of breast cancer patients who may benefit from BET inhibitors without the risk of diminishing the anti-tumoral immune activity.
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