Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer
Abstract Cancer-associated fibroblasts (CAFs) are highly heterogeneous cells and important components of the breast tumor microenvironment (TME). However, their role and clinical value in ER-positive breast cancer have not been fully clarified. Our study aims to comprehensively characterize the hete...
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2025-03-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03705-1 |
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| author | Zhi-Hao Yu Huan-Ling Xu Shuo Wang Ying-Xi Li Gui-Xin Wang Yao Tian Zhao-Hui Chen Wen-Bin Song Long He Xin Wang Xu-Chen Cao Yue Yu |
| author_facet | Zhi-Hao Yu Huan-Ling Xu Shuo Wang Ying-Xi Li Gui-Xin Wang Yao Tian Zhao-Hui Chen Wen-Bin Song Long He Xin Wang Xu-Chen Cao Yue Yu |
| author_sort | Zhi-Hao Yu |
| collection | DOAJ |
| description | Abstract Cancer-associated fibroblasts (CAFs) are highly heterogeneous cells and important components of the breast tumor microenvironment (TME). However, their role and clinical value in ER-positive breast cancer have not been fully clarified. Our study aims to comprehensively characterize the heterogeneity, potential biological functions, and molecular mechanisms of CAFs in ER-positive breast cancer within the tumor microenvironment using multi-omics data, to provide new strategies for the diagnosis and treatment of ER-positive breast cancer patients. In this study, we found that COL1A2(+) MMP1(+) and COL1A2(+) MMP1(-) CAFs were associated with unfavorable prognosis. The dynamic evolution and cell-cell communications of CAFs were analyzed, revealing that COL1A2(+) MMP1(+/-) CAFs show extensive crosstalk with tumor-associated macrophages (TAMs), contributing to an immunosuppressive TME. Moreover, the somatic mutation of TP53 may be a potential indicator for evaluating the infiltration of COL1A2(+) MMP1(+/-) CAFs. Finally, an MRI-based radiomic model was constructed to estimate the abundance of these CAFs. In conclusion, our findings provide a theoretical basis for targeting CAFs and offer a noninvasive approach to evaluate the infiltration level of COL1A2(+) MMP1(+/-) CAFs. |
| format | Article |
| id | doaj-art-a9d8da3239574985b5112053cbf8c5f3 |
| institution | DOAJ |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-a9d8da3239574985b5112053cbf8c5f32025-08-20T03:05:49ZengBMCCancer Cell International1475-28672025-03-0125111610.1186/s12935-025-03705-1Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancerZhi-Hao Yu0Huan-Ling Xu1Shuo Wang2Ying-Xi Li3Gui-Xin Wang4Yao Tian5Zhao-Hui Chen6Wen-Bin Song7Long He8Xin Wang9Xu-Chen Cao10Yue Yu11The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerImmunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerThe First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerAbstract Cancer-associated fibroblasts (CAFs) are highly heterogeneous cells and important components of the breast tumor microenvironment (TME). However, their role and clinical value in ER-positive breast cancer have not been fully clarified. Our study aims to comprehensively characterize the heterogeneity, potential biological functions, and molecular mechanisms of CAFs in ER-positive breast cancer within the tumor microenvironment using multi-omics data, to provide new strategies for the diagnosis and treatment of ER-positive breast cancer patients. In this study, we found that COL1A2(+) MMP1(+) and COL1A2(+) MMP1(-) CAFs were associated with unfavorable prognosis. The dynamic evolution and cell-cell communications of CAFs were analyzed, revealing that COL1A2(+) MMP1(+/-) CAFs show extensive crosstalk with tumor-associated macrophages (TAMs), contributing to an immunosuppressive TME. Moreover, the somatic mutation of TP53 may be a potential indicator for evaluating the infiltration of COL1A2(+) MMP1(+/-) CAFs. Finally, an MRI-based radiomic model was constructed to estimate the abundance of these CAFs. In conclusion, our findings provide a theoretical basis for targeting CAFs and offer a noninvasive approach to evaluate the infiltration level of COL1A2(+) MMP1(+/-) CAFs.https://doi.org/10.1186/s12935-025-03705-1Cancer-associated fibroblastsRadiomicsER-positive breast cancerTumor microenvironmentSingle-cell RNA sequencing |
| spellingShingle | Zhi-Hao Yu Huan-Ling Xu Shuo Wang Ying-Xi Li Gui-Xin Wang Yao Tian Zhao-Hui Chen Wen-Bin Song Long He Xin Wang Xu-Chen Cao Yue Yu Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer Cancer Cell International Cancer-associated fibroblasts Radiomics ER-positive breast cancer Tumor microenvironment Single-cell RNA sequencing |
| title | Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer |
| title_full | Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer |
| title_fullStr | Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer |
| title_full_unstemmed | Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer |
| title_short | Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer |
| title_sort | integrating spatial and single cell transcriptomes reveals the role of col1a2 mmp1 cancer associated fibroblasts in er positive breast cancer |
| topic | Cancer-associated fibroblasts Radiomics ER-positive breast cancer Tumor microenvironment Single-cell RNA sequencing |
| url | https://doi.org/10.1186/s12935-025-03705-1 |
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