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<p>Breast cancers are biologically and clinically diverse. While large-scale gene expression analyses have enabled epithelial-centered molecular classifications, studies of the tumor microenvironment (TME) remain limited, especially at the proteome level using tissue-specific resolution. By laser capture microdissection and mass spectrometry-based proteomics followed by unsupervised clustering of the stromal proteome, we discovered three patient subgroups. The largest cluster revealed the most discrete representation of stromal proteins, including a 35-protein (35P) panel linked to extracellular matrix biology, tumor progression programs, and increased abundance of tumor-associated macrophages (TAM) by single-cell profiling. Clinical validation of 35P, using whole tissue protein and mRNA values from different cohorts of ER+/HER2− breast cancer, including a large randomized controlled trial (STO), identified that more aggressive (or ‘high-grade’) stromal features were independent of current molecular subtypes. The 35P stromal panel may reflect important clinical information by improving patient stratification beyond current epithelial-based classification of breast cancer.</p>

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Stromal-based proteome data improve stratification of hormone receptor-positive breast cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月9日

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  • Kenneth Finne,
  • Silje Kjølle,
  • Magdalena Ríos Romero,
  • Even Birkeland,
  • Heidrun Vethe,
  • Sura Aziz,
  • Gøril Knutsvik,
  • Elisabeth Wik,
  • Linda Sofie Lindström,
  • Lars A. Akslen

摘要

Breast cancers are biologically and clinically diverse. While large-scale gene expression analyses have enabled epithelial-centered molecular classifications, studies of the tumor microenvironment (TME) remain limited, especially at the proteome level using tissue-specific resolution. By laser capture microdissection and mass spectrometry-based proteomics followed by unsupervised clustering of the stromal proteome, we discovered three patient subgroups. The largest cluster revealed the most discrete representation of stromal proteins, including a 35-protein (35P) panel linked to extracellular matrix biology, tumor progression programs, and increased abundance of tumor-associated macrophages (TAM) by single-cell profiling. Clinical validation of 35P, using whole tissue protein and mRNA values from different cohorts of ER+/HER2− breast cancer, including a large randomized controlled trial (STO), identified that more aggressive (or ‘high-grade’) stromal features were independent of current molecular subtypes. The 35P stromal panel may reflect important clinical information by improving patient stratification beyond current epithelial-based classification of breast cancer.