Deciphering the association of spatial landscapes of DCIS with recurrence as invasive breast cancer
Graham, N.; Turnbull, A. K.; Martinez-Perez, C.; Dixon, M.; Petitprez, F.; Kitamura, T.
Show 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.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Extracellular matrix rigidity controls breast cancer metastasis via TYK2-mediated mechanotransduction 95%
- CXCR3-expressing metastasis-initiating cells induce and exploit a fibroblast niche in the lungs to fuel metastatic colonization 95%
- Multiplexed RNA-FISH-guided Laser Capture Microdissection RNA Sequencing Improves Breast Cancer Molecular Subtyping, Prognostic Classification, and Predicts Response to Antibody Drug Conjugates 95%
Similar papers in this journal
- Lineage plasticity enables low-ER luminal tumors to evolve and gain basal-like traits 95%
- Mutational landscape of pure ductal carcinoma in situ and associations with disease prognosis and response to radiotherapy 95%
- Evolutionary Measures Show that Recurrence of DCIS is Distinct from Progression to Breast Cancer 94%
Similar papers in this journal
- The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer 95%
- HIF-1 regulated TPM3 links hypoxia to motility and invasion beyond the hypoxic fraction in triple-negative breast cancer 95%
- The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.