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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| Format: | Article |
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eLife Sciences Publications Ltd
2025-06-01
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| Online Access: | https://elifesciences.org/articles/100923 |
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| author | Xuantong Gong Lishuang Gu Di Yang Yu He Qian Li Hao Qin Yong Wang |
| author_facet | Xuantong Gong Lishuang Gu Di Yang Yu He Qian Li Hao Qin Yong Wang |
| author_sort | Xuantong Gong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9f01969c3e2a4a4bbefc1d38faab0754 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-9f01969c3e2a4a4bbefc1d38faab07542025-08-20T02:23:41ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011310.7554/eLife.100923Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysisXuantong Gong0https://orcid.org/0000-0001-8984-5461Lishuang Gu1https://orcid.org/0000-0003-0746-5620Di Yang2https://orcid.org/0000-0002-3521-8371Yu He3Qian Li4https://orcid.org/0000-0003-0182-3634Hao Qin5Yong Wang6https://orcid.org/0000-0001-7682-0433Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Ultrasound, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, ChinaDepartment of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Ultrasound, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, ChinaKey Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Ultrasound, The First Affiliated Hospital of China Medical University, Shenyang, Shenyang, ChinaTriple-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.https://elifesciences.org/articles/100923RNA-seqferroptosistumor microenvironmenttriple-negative breast cancer |
| spellingShingle | Xuantong Gong Lishuang Gu Di Yang Yu He Qian Li Hao Qin Yong Wang Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis eLife RNA-seq ferroptosis tumor microenvironment triple-negative breast cancer |
| title | Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis |
| title_full | Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis |
| title_fullStr | Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis |
| title_full_unstemmed | Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis |
| title_short | Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis |
| title_sort | ferroptosis related genes mediate tumor microenvironment and prognosis in triple negative breast cancer via integrated rna seq analysis |
| topic | RNA-seq ferroptosis tumor microenvironment triple-negative breast cancer |
| url | https://elifesciences.org/articles/100923 |
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