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Identification of CHD4-β1 integrin axis as a prognostic marker in triple-negative breast cancer using next-generation
Fu Ou-Yang1, Mei-Ren Pan2, Shu-Jyuan Chang3
1Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Aims:
Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that lacks receptor expression and is difficult to cure. Epigenetic regulators have been suggested as targets for cancer therapy in recent years. Our previous study indicated that the chromodomain-helicase-DNA-binding protein 4 (CHD4) is a prognostic biomarker of TNBC and therapeutic target in patients with TNBC. However, the exact mechanisms regulated by CHD4 are still unclear.
Methods:
In this study, we compared differences in gene expression in parental and CHD4-deficient cells by next-generation sequencing and Ingenuity Pathway Analysis.
Key Findings:
We found that β1 integrin is a downstream target gene of CHD4, which could be transcriptionally regulated by CHD4 in TNBC cells. Consistent with in vitro data, immunohistochemistry revealed that co-expression of β1 integrin and CHD4 was significantly associated with metastatic state, recurrence, and survival status in TNBC patients. It also showed a positive correlation between β1 integrin and CHD4 in vivo.
Significance:
This is the first study to suggest that CHD4 regulates β1 integrin in TNBC. Overall, CHD4-β1 integrin axis could potentially be a predictive marker in patients with TNBC and the use of β1 integrin inhibitors may be a therapeutic option for TNBC patients with high CHD4 expression.
Insights
Chromodomain-helicase-DNA-binding protein 4 (CHD4) regulates β1 integrin in triple-negative breast cancer (TNBC). This CHD4-β1 integrin axis may serve as a predictive marker and therapeutic target for TNBC patients.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Epigenetic regulators are emerging as potential cancer targets.
- Chromodomain-helicase-DNA-binding protein 4 (CHD4) is a previously identified prognostic biomarker and therapeutic target in TNBC.
Purpose of the Study:
- To elucidate the underlying mechanisms by which CHD4 influences TNBC.
- To investigate the relationship between CHD4 and its downstream targets in TNBC.
Main Methods:
- Gene expression profiling using next-generation sequencing.
- Bioinformatic analysis with Ingenuity Pathway Analysis (IPA).
- In vitro and in vivo validation using cell lines and patient samples (immunohistochemistry).
Main Results:
- CHD4 was found to transcriptionally regulate β1 integrin in TNBC cells.
- Co-expression of β1 integrin and CHD4 correlated significantly with metastatic status, recurrence, and survival in TNBC patients.
- A positive correlation between β1 integrin and CHD4 was observed in vivo.
Conclusions:
- This study establishes CHD4 as a regulator of β1 integrin in TNBC.
- The CHD4-β1 integrin axis presents a potential predictive biomarker for TNBC.
- Targeting β1 integrin may offer a therapeutic strategy for TNBC patients with high CHD4 expression.
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