Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis
Triple-negative breast cancer (TNBC), an aggressive malignancy with limited tools to predict recurrence and drug sensitivity, exhibits ferroptotic heterogeneity across subtypes. However, the tumor microenvironment (TME) mediated by ferroptosis-related genes remains poorly characterized. This study i...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2025-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/100923 |
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| Summary: | Triple-negative breast cancer (TNBC), an aggressive malignancy with limited tools to predict recurrence and drug sensitivity, exhibits ferroptotic heterogeneity across subtypes. However, the tumor microenvironment (TME) mediated by ferroptosis-related genes remains poorly characterized. This study integrates single-cell and bulk RNA sequencing data from the Gene Expression Omnibus to elucidate ferroptosis-driven TME features in TNBC, employing machine learning to develop prognostic and therapeutic response prediction models. At the single-cell level, T cells were classified into three subpopulations and macrophages into two subpopulations, with their infiltration degrees significantly correlated with clinical outcomes. A risk score model constructed based on these findings demonstrated robust predictive performance, validated in external cohorts with 3-, 4-, and 5-year area under the receiver operating characteristic curves of 0.65, 0.67, and 0.71, respectively. Notably, high-risk patients exhibited enhanced sensitivity to 27 therapeutic agents. By delineating ferroptosis-associated immune heterogeneity, this work provides a risk stratification tool to enhance prognostic precision and therapeutic decision-making in TNBC, while identifying genes offer actionable targets for TNBC precision medicine. |
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| ISSN: | 2050-084X |