Evaluation of Genes and Molecular Pathways Involved in Ferroptosis in Breast Cancer: A Systems Biology and Bioinformatics Approach Publisher



Heydari A ; Yaghmoorian Khojini J ; Hayati MJ ; Khara F ; Abootorabi SMS ; Manoochehri H ; Mousavi MJ
Source: Biochemistry and Biophysics Reports Published:2025

Abstract

Background Breast cancer (BC) is a leading cause of cancer mortality worldwide. Ferroptosis, an unique form of iron-dependent cell death, has emerged as a promising therapeutic target to overcome drug resistance. This study aimed to identify key ferroptosis-related genes and their regulatory pathways that are dysregulated in BC. Methods Through a systems biology approach, we analyzed gene expression data from two independent GEO datasets. We identified differentially expressed genes (DEGs) in tumor versus normal tissues and intersected them with a curated database of ferroptosis regulators to define a high-confidence list of Ferroptosis-related DEGs (FeffDEGs). Subsequently, we performed functional enrichment, protein-protein interaction (PPI) network analysis to identify hub genes, and explored their potential regulatory miRNAs and transcription factors (TFs). Results We identified 73 FeffDEGs significantly enriched in pathways related to oxidative stress and lipid metabolism. Seven hub genes were pinpointed, including the upregulated oncogene EZH2 and the downregulated tumor suppressor PTEN . Further analysis revealed that these hub genes are potentially regulated by key molecules such as hsa-miR-137, hsa-miR-429 and the transcription factor AR. Conclusions Our findings highlight that hub genes like EZH2 and PTEN are potential biomarkers and therapeutic targets for modulating ferroptosis in breast cancer. These results provide a strong foundation for future experimental validation to translate computational insights into clinical applications. © 2025 Elsevier B.V., All rights reserved.