Deciphering the association of spatial landscapes of DCIS with recurrence as invasive breast cancer
- 1Centre for Reproductive Health, Institute of Regeneration and Repair, University of Edinburgh
Abstract
Stromal cell composition has been proposed as a potential biomarker in ductal carcinoma in situ (DCIS) for assessing the risk of subsequent recurrence or progression to invasive breast cancer (IBC). However, the characteristics of the tumor microenvironment within DCIS associated with these outcomes remain poorly understood. Here, we perform spatial transcriptomic analyses of 49 primary DCIS specimens from patients with no recurrence, DCIS recurrence, or recurrence as IBC. Cell mapping reveals spatially organized stromal cell gradients within DCIS, with enrichment of TREM2+ macrophages and myofibroblastic cancer-associated fibroblasts (myCAFs) in tumor-proximal niches. Notably, the abundance of TREM2+ macrophages near tumor nests is associated with subsequent recurrence as IBC. Moreover, ligand-receptor pair analysis identifies GRN--SORT1, SPP1--CD44, and LGALS9--CD44 interactions as spatially plausible signaling interactions between TREM2+ macrophages and epithelial cells. Finally, these findings are validated at the protein level by multiplex immunostaining of serial sections. This study characterizes the spatial landscape of the DCIS tumor microenvironment associated with subsequent recurrence, providing a basis for developing biomarkers of disease progression and identifying potential therapeutic targets.
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BibTeX
@misc{graham2026deciphering,
title = {{Deciphering the association of spatial landscapes of DCIS with recurrence as invasive breast cancer}},
author = {N. Graham and A. K. Turnbull and C. Martinez-Perez and M. Dixon and F. Petitprez and T. Kitamura},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754326},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754326v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Deciphering the association of spatial landscapes of DCIS with recurrence as invasive breast cancer
AU - N. Graham
AU - A. K. Turnbull
AU - C. Martinez-Perez
AU - M. Dixon
AU - F. Petitprez
AU - T. Kitamura
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754326
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754326v1
AB - Stromal cell composition has been proposed as a potential biomarker in ductal carcinoma in situ (DCIS) for assessing the risk of subsequent recurrence or progression to invasive breast cancer (IBC). However, the characteristics of the tumor microenvironment within DCIS associated with these outcomes remain poorly understood. Here, we perform spatial transcriptomic analyses of 49 primary DCIS specimens from patients with no recurrence, DCIS recurrence, or recurrence as IBC. Cell mapping reveals spatially organized stromal cell gradients within DCIS, with enrichment of TREM2+ macrophages and myofibroblastic cancer-associated fibroblasts (myCAFs) in tumor-proximal niches. Notably, the abundance of TREM2+ macrophages near tumor nests is associated with subsequent recurrence as IBC. Moreover, ligand-receptor pair analysis identifies GRN--SORT1, SPP1--CD44, and LGALS9--CD44 interactions as spatially plausible signaling interactions between TREM2+ macrophages and epithelial cells. Finally, these findings are validated at the protein level by multiplex immunostaining of serial sections. This study characterizes the spatial landscape of the DCIS tumor microenvironment associated with subsequent recurrence, providing a basis for developing biomarkers of disease progression and identifying potential therapeutic targets.
ER -