CXCL1 Clone Evolution Induced by the HDAC Inhibitor Belinostat Might Be a Favorable Prognostic Indicator in...

Area of Science:

• Oncology
• Epigenetics
• Genomics

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options and frequent chemotherapy resistance.
• Histone deacetylase inhibitors (HDACis), effective in lymphoma, show poor efficacy in solid tumors, with resistance mechanisms poorly understood.

Purpose of the Study:

• To investigate the molecular mechanisms underlying belinostat (an HDACi) resistance in TNBC.
• To identify key genes and pathways affected by belinostat treatment in TNBC.
• To explore the prognostic significance of identified genes in breast cancer survival.

Main Methods:

• Analysis of the GSE129944 microarray dataset for differentially expressed genes (DEGs) in TNBC cells treated with belinostat.
• Gene Ontology (GO) and KEGG pathway enrichment analyses.
• Protein-protein interaction (PPI) network construction and analysis.
• In vitro validation in additional TNBC cell lines.

Main Results:

• Identified 465 DEGs (240 downregulated, 225 upregulated) in belinostat-treated TNBC cells.
• The cytokine-cytokine receptor interaction pathway was significantly altered.
• CXCL1 expression was associated with favorable overall survival in breast cancer patients.
• Belinostat treatment induced CXCL1 expression in multiple TNBC cell lines.

Conclusions:

• Belinostat-induced CXCL1 expression may be linked to cellular stress and evolution under HDACi treatment.
• Findings suggest a novel perspective on clone evolution during HDACi therapy for TNBC.
• Potential implications for implementing diverse mutation-targeted treatments throughout the therapeutic cycle.