Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis
Abstract Objectives Breast cancer patients with diabetes are often associated with poor prognosis. This study aims to investigate the role of metformin in ferroptosis and cuproptosis in diabetic breast cancer patients and explore its potential impact on clinical outcomes. Methods We retrospectively...
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| Format: | Article |
| Language: | English |
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Springer
2025-04-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02425-2 |
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| author | Changwen Li Tao Chen Yuanyuan Li Chunyan Zhou Jing Du Xiaoxin Li Chuangang Tang Cheng Ma Na Deng Huaixin Cui |
| author_facet | Changwen Li Tao Chen Yuanyuan Li Chunyan Zhou Jing Du Xiaoxin Li Chuangang Tang Cheng Ma Na Deng Huaixin Cui |
| author_sort | Changwen Li |
| collection | DOAJ |
| description | Abstract Objectives Breast cancer patients with diabetes are often associated with poor prognosis. This study aims to investigate the role of metformin in ferroptosis and cuproptosis in diabetic breast cancer patients and explore its potential impact on clinical outcomes. Methods We retrospectively analyzed tissue samples from 16 breast cancer patients, including 5 non-diabetic and 11 diabetic patients (6 treated with metformin). Immunohistochemistry (IHC) staining was performed for cuproptosis (FDX1, DLAT), ferroptosis (ACSL4, GPX4), and glycolysis markers (LDHA, PKM2). Statistical analysis used quantitative results from immunohistochemistry. Results Patients treated with metformin showed significantly higher expression of FDX1 and ACSL4, along with a significant decrease in GPX4 compared to other groups. Kaplan–Meier survival analysis revealed that high FDX1 expression was associated with longer survival in breast cancer patients. Correlation analysis showed a positive association between ACSL4 and FDX1 (R = 0.51, P = 0.045), suggesting a relationship between these markers. Conclusions Metformin may simultaneously enhance both cuproptosis and ferroptosis in breast cancer. FDX1 expression could serve as a prognostic marker for survival, especially in diabetic patients, providing insights into targeting metabolic and cell death pathways in breast cancer therapy. |
| format | Article |
| id | doaj-art-dbcd8b0309c54ed9ab5a8cbf79d62473 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-dbcd8b0309c54ed9ab5a8cbf79d624732025-08-20T03:52:19ZengSpringerDiscover Oncology2730-60112025-04-0116111110.1007/s12672-025-02425-2Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysisChangwen Li0Tao Chen1Yuanyuan Li2Chunyan Zhou3Jing Du4Xiaoxin Li5Chuangang Tang6Cheng Ma7Na Deng8Huaixin Cui9The Affiliated Xuzhou Clinical College of Xuzhou Medical UniversityThe Affiliated Xuzhou Clinical College of Xuzhou Medical UniversityThe Affiliated Xuzhou Clinical College of Xuzhou Medical UniversityThe Affiliated Xuzhou Clinical College of Xuzhou Medical UniversitySchool of Life Sciences, Jiangsu Normal UniversityDepartment of Pathology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical College of Southeast UniversityDepartment of Breast Surgery, Xuzhou Central HospitalDepartment of Gastrointestinal Surgery, Xuzhou Central HospitalDepartment of Breast Surgery, Xuzhou Central HospitalThe Affiliated Xuzhou Clinical College of Xuzhou Medical UniversityAbstract Objectives Breast cancer patients with diabetes are often associated with poor prognosis. This study aims to investigate the role of metformin in ferroptosis and cuproptosis in diabetic breast cancer patients and explore its potential impact on clinical outcomes. Methods We retrospectively analyzed tissue samples from 16 breast cancer patients, including 5 non-diabetic and 11 diabetic patients (6 treated with metformin). Immunohistochemistry (IHC) staining was performed for cuproptosis (FDX1, DLAT), ferroptosis (ACSL4, GPX4), and glycolysis markers (LDHA, PKM2). Statistical analysis used quantitative results from immunohistochemistry. Results Patients treated with metformin showed significantly higher expression of FDX1 and ACSL4, along with a significant decrease in GPX4 compared to other groups. Kaplan–Meier survival analysis revealed that high FDX1 expression was associated with longer survival in breast cancer patients. Correlation analysis showed a positive association between ACSL4 and FDX1 (R = 0.51, P = 0.045), suggesting a relationship between these markers. Conclusions Metformin may simultaneously enhance both cuproptosis and ferroptosis in breast cancer. FDX1 expression could serve as a prognostic marker for survival, especially in diabetic patients, providing insights into targeting metabolic and cell death pathways in breast cancer therapy.https://doi.org/10.1007/s12672-025-02425-2Breast cancerMetforminCuproptosisFerroptosisDiabetesGlycolysis |
| spellingShingle | Changwen Li Tao Chen Yuanyuan Li Chunyan Zhou Jing Du Xiaoxin Li Chuangang Tang Cheng Ma Na Deng Huaixin Cui Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis Discover Oncology Breast cancer Metformin Cuproptosis Ferroptosis Diabetes Glycolysis |
| title | Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis |
| title_full | Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis |
| title_fullStr | Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis |
| title_full_unstemmed | Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis |
| title_short | Impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients: an immunohistochemical analysis |
| title_sort | impact of diabetes and metformin on cuproptosis and ferroptosis in breast cancer patients an immunohistochemical analysis |
| topic | Breast cancer Metformin Cuproptosis Ferroptosis Diabetes Glycolysis |
| url | https://doi.org/10.1007/s12672-025-02425-2 |
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