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Introduction <p>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited therapeutic options. Mesothelin (MSLN), a tumor-associated antigen with potential targeted drugs, has been reported to be positive in some TNBC patients. However, there is a lack of studies on the clinicopathological characteristics of MSLN-expressing TNBC.</p> Materials and methods <p>We first demonstrated the significance of MSLN through pan-cancer analysis. We utilized local cohort to demonstrated that MSLN is associated with an immunosuppressive microenvironment and patients with high MSLN expression have poorer response to neoadjuvant chemotherapy combined with immunotherapy. Moreover, MSLN-expressing TNBC exhibit extensive lymphovascular tumor thrombi. Furthermore, spatial transcriptomics investigated T1N3-stage TNBC and identified MSLN as a highly expressed target in this aggressive subtype, public single-cell data identified MSLN-expressing tumor sub-cluster and their characteristics.</p> Conclusion <p>This study provides novel insights into the role of MSLN in TNBC and lays the foundation for future therapeutic strategies targeting MSLN in this aggressive breast cancer subtype.</p>

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Mesothelin-expressing triple-negative breast cancer: a highly invasive and immunosuppressive subtype

  • 期刊论文

  • 发表日期：

    2025年11月25日

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  • Zuxuan Zhao,
  • Huizi Lei,
  • Bingzhi Wang,
  • Lei Guo,
  • Lina Gao,
  • Bingning Wang,
  • Shan Zheng,
  • Jianming Ying

摘要

Introduction

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited therapeutic options. Mesothelin (MSLN), a tumor-associated antigen with potential targeted drugs, has been reported to be positive in some TNBC patients. However, there is a lack of studies on the clinicopathological characteristics of MSLN-expressing TNBC.

Materials and methods

We first demonstrated the significance of MSLN through pan-cancer analysis. We utilized local cohort to demonstrated that MSLN is associated with an immunosuppressive microenvironment and patients with high MSLN expression have poorer response to neoadjuvant chemotherapy combined with immunotherapy. Moreover, MSLN-expressing TNBC exhibit extensive lymphovascular tumor thrombi. Furthermore, spatial transcriptomics investigated T1N3-stage TNBC and identified MSLN as a highly expressed target in this aggressive subtype, public single-cell data identified MSLN-expressing tumor sub-cluster and their characteristics.

Conclusion

This study provides novel insights into the role of MSLN in TNBC and lays the foundation for future therapeutic strategies targeting MSLN in this aggressive breast cancer subtype.