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Published on: February 21, 2014
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.
Introduction:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a potential therapeutic target. This study aimed to evaluate the expression levels of ferroptosis-associated genes GPX4, ACSL4, and BCAT2 in TNBC tissues and to investigate their potential as diagnostic or therapeutic biomarkers.
Material And Methods:
A total of 100 formalin-fixed paraffin-embedded (FFPE) breast tissue samples were analyzed, including 60 TNBC patient samples and 40 healthy controls. Gene expression levels of GPX4, ACSL4, and BCAT2 were determined using RT-qPCR. Statistical comparisons were conducted using the Mann-Whitney U test, and correlation analyses were performed using Spearman's test.
Results:
The expression levels of GPX4, ACSL4, and BCAT2 were significantly lower in the TNBC group compared to controls (p = 0.0001 for all genes). Strong positive correlations were observed among the three genes, with BCAT2 showing the highest correlation with both GPX4 (R = 0.636) and ACSL4 (R = 0.683). Additionally, BCAT2 expression negatively correlated with tumor diameter and Ki-67 index.
Conclusions:
The significant downregulation and strong positive correlation of GPX4, ACSL4, and BCAT2 in TNBC tissues suggest coordinated suppression of ferroptosis. These findings highlight the potential of targeting ferroptosis as a novel therapeutic strategy in TNBC and propose these genes as candidate biomarkers for diagnosis and treatment response.
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.
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