Authors
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
Published in
Nature communications. Jul 02, 2026. Epub Jul 02, 2026.
Abstract
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.
PMID:
42393057
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.
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