ArticleBiochemistry and biophysics reports2025
Integrated bioinformatics analysis identifies cuproptosis and ferroptosis gene signatures via subgroup clustering: Prognostic and therapeutic implications in breast cancer.
Article in Biochemistry and biophysics reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Computational identification of putative mRNA-miRNA signatures in chemoresistant and metastatic triple-negative breast cancer.Biochemistry and biophysics reports · 2026Article
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3 authors.
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Abstract
Objective: This study aimed to investigate the prognostic value and biological implications of cuproptosis/ferroptosis-related genes in breast cancer, and to develop a robust molecular signature for risk stratification and treatment guidance. Methods: Integrative bioinformatic analysis of TCGA and GEO datasets identified cuproptosis/ferroptosis-related genes. LASSO and Cox regression were used to refine a multi-gene signature. Unsupervised clustering stratified molecular subtypes. Genomic alterations, immune microenvironment composition, and drug sensitivity were assessed using bioinformatic tools. Experimental validation included immunohistochemistry and Western blot using clinical samples and cell lines (MCF-10A, MDA-MB-231, BT-549, SKBR-3, MCF-7). Results: A four-gene signature (MTDH, PROM2, IFNG, SLC1A4) with independent prognostic value was established. Subtype-specific expression patterns emerged: IFNG associated with basal-like tumors and cytotoxic immunity, while SLC1A4 (HER2-enriched/luminal) and MTDH/PROM2 correlated with immunosuppressive microenvironments. Disease progression showed stage-dependent attenuation of IFNG/MTDH/PROM2 and progressive SLC1A4 upregulation. Genomic profiling revealed recurrent mutations and frequent copy-number amplifications, notably of MTDH (60.37 %) and loci on chromosomes 2/3. Functional assays demonstrated IFNG/MTDH/SLC1A4-mediated resistance to anthracyclines and microtubule inhibitors, contrasting with PROM2-associated chemosensitivity. Unsupervised clustering identified two molecular subtypes with divergent survival, characterized by distinct pathway activation. Prognostic nomograms achieved robust predictive accuracy (C-index: 0.755). Validation confirmed upregulation of all four genes in breast cancer. Conclusion: The cuproptosis/ferroptosis-related genes-based signature serves as a reliable prognostic tool, reflecting immune landscape remodeling and genomic instability in BRCA. These findings provide insights into subtype-specific therapeutic vulnerabilities and suggest potential strategies for targeting cuproptosis/ferroptosis pathways in precision oncology.
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