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<p>The progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) critically determines patient outcomes, yet its mechanisms remain incompletely understood. Integrating single-cell RNA sequencing, spatial transcriptomics, and genomics across 28 patients with synchronous DCIS and IBC, we delineate the spatial-molecular hierarchy of this transition. Invasion is primarily driven by clonal expansion of pre-existing DCIS subclones, emphasizing transcriptional reprogramming and tumor microenvironment (TME) remodeling over acquisition of additional driver alterations. IBC cells exhibit pronounced epithelial-mesenchymal transition and metabolic reprogramming. We uncover dynamic TME remodeling at the invasive front, identifying key ligand–receptor interactions (e.g., PPIA-BSG, MDK-LRP1, CXCL12-CXCR4) facilitating basement membrane disruption, angiogenesis and immunosuppression. Deconvolution of basement membrane breach reveals four molecularly defined stages (NMFT1–NMFT4) with progressively worsening patient survival. This study establishes a unified spatial-molecular atlas of DCIS-IBC progression, highlighting clonal expansion, transcriptional plasticity and TME remodeling as key drivers of invasion.</p>

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Single cell spatial transcriptomics track the evolutionary hierarchy and microenvironment remodeling during breast carcinoma invasion

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月2日

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  • Di Wang,
  • Qichen Dai,
  • Jingwen Guo,
  • Dan Li,
  • Changyuan Guo,
  • Peiqing Ma,
  • Feng Wen,
  • Xiangyu Tong,
  • Changhao Gong,
  • Han Cheng,
  • Meng Li,
  • Ranjiaxi Wang,
  • Jianlin Liu,
  • Yingying Feng,
  • Fengpu Fan,
  • Xiaoqian Shi,
  • Qian Zhang,
  • Xingmei Shu,
  • Yu Sun,
  • Xunan Shen,
  • Ziqing Deng,
  • Jiaqi Liu,
  • Fei Ma,
  • Yipeng Wang,
  • Lin Feng

摘要

The progression from ductal carcinoma in situ (DCIS) to invasive breast carcinoma (IBC) critically determines patient outcomes, yet its mechanisms remain incompletely understood. Integrating single-cell RNA sequencing, spatial transcriptomics, and genomics across 28 patients with synchronous DCIS and IBC, we delineate the spatial-molecular hierarchy of this transition. Invasion is primarily driven by clonal expansion of pre-existing DCIS subclones, emphasizing transcriptional reprogramming and tumor microenvironment (TME) remodeling over acquisition of additional driver alterations. IBC cells exhibit pronounced epithelial-mesenchymal transition and metabolic reprogramming. We uncover dynamic TME remodeling at the invasive front, identifying key ligand–receptor interactions (e.g., PPIA-BSG, MDK-LRP1, CXCL12-CXCR4) facilitating basement membrane disruption, angiogenesis and immunosuppression. Deconvolution of basement membrane breach reveals four molecularly defined stages (NMFT1–NMFT4) with progressively worsening patient survival. This study establishes a unified spatial-molecular atlas of DCIS-IBC progression, highlighting clonal expansion, transcriptional plasticity and TME remodeling as key drivers of invasion.