Triple-negative breast cancer and ferroptosis: expression profiling of key regulatory genes

Serife E Antmen1, Cem Yalaza2, Ferah Tuncel3

  • 1Department of Biochemistry, Faculty of Pharmacy, Mersin University, Mersin, Turkey.

PubMed
Abstract

Insights

Expression of ferroptosis genes GPX4, ACSL4, and BCAT2 is significantly reduced in triple-negative breast cancer (TNBC). These genes show strong correlations and may serve as biomarkers for TNBC diagnosis and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression.
  • Ferroptosis, a cell death pathway involving lipid peroxidation, is a potential therapeutic target for TNBC.

Purpose of the Study:

  • To evaluate ferroptosis-associated gene expression (GPX4, ACSL4, BCAT2) in TNBC tissues.
  • To investigate the diagnostic and therapeutic potential of these genes as biomarkers.

Main Methods:

  • Analysis of 100 breast tissue samples (60 TNBC, 40 controls) using formalin-fixed paraffin-embedded (FFPE) tissues.
  • Quantification of GPX4, ACSL4, and BCAT2 gene expression via RT-qPCR.
  • Statistical analysis including Mann-Whitney U test and Spearman's correlation.

Main Results:

  • Significantly lower expression of GPX4, ACSL4, and BCAT2 in TNBC compared to controls (p=0.0001).
  • Strong positive correlations observed among GPX4, ACSL4, and BCAT2 (BCAT2 highest correlation).
  • BCAT2 expression negatively correlated with tumor diameter and Ki-67 index.

Conclusions:

  • Coordinated suppression of ferroptosis indicated by downregulated ferroptosis genes in TNBC.
  • GPX4, ACSL4, and BCAT2 show potential as biomarkers for TNBC diagnosis and treatment response.
  • Targeting ferroptosis presents a novel therapeutic strategy for TNBC.