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<p>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 <i>COL1A2</i>(+) <i>MMP1</i>(+) and <i>COL1A2</i>(+) <i>MMP1</i>(-) CAFs were associated with unfavorable prognosis. The dynamic evolution and cell-cell communications of CAFs were analyzed, revealing that <i>COL1A2</i>(+) <i>MMP1</i>(+/-) CAFs show extensive crosstalk with tumor-associated macrophages (TAMs), contributing to an immunosuppressive TME. Moreover, the somatic mutation of <i>TP53</i> may be a potential indicator for evaluating the infiltration of <i>COL1A2</i>(+) <i>MMP1</i>(+/-) 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 <i>COL1A2</i>(+) <i>MMP1</i>(+/-) CAFs.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月7日

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  • 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

摘要

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.