Identification of CHD4-β1 integrin axis as a prognostic marker in triple-negative breast cancer using next-generation sequencing and bioinformatics

Abstract

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.

Keywords: CHD4; Ingenuity pathway analysis; Next-generation sequencing; Triple-negative breast cancer; β1 integrin.