Integrating spatial and single-cell transcriptomes reveals the role of COL1A2(+) MMP1(+/-) cancer-associated fibroblasts in ER-positive breast cancer

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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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Cancer Cell International
Subjects:
Cancer-associated fibroblasts
Radiomics
ER-positive breast cancer
Tumor microenvironment
Single-cell RNA sequencing
Online Access:https://doi.org/10.1186/s12935-025-03705-1
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Summary: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.
ISSN:1475-2867

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