Document Type
Article
Publication Date
1-27-2026
Publication Title
Cell Reports
Abstract
Triple-negative breast cancer (TNBC) is a prevalent breast cancer subtype with the lowest 5-year survival. Several factors influence outcomes, but their inherent molecular and cellular heterogeneity are increasingly acknowledged as crucial determinants. Here, we report on the spatio-molecular heterogeneity underlying TNBC tumors in a retrospective, treatment-naive cohort with differential prognoses (17 good prognoses [GPx] >15-year survival and 15 poor prognoses [PPx] < 3-year survival]) profiled using GeoMx Digital Spatial Profiler. Analyses reveal that epithelial and microenvironment (TME) states are transcriptionally distinct between groups. Invasive GPx epithelia show an increase in immune transcripts, with a more immune-rich TME (via IF). PPx epithelia, in contrast, are more metabolically and translationally active, with a mesenchymal/fibrotic TME. Pre-cancerous epithelia in PPx exhibit a presence of aggressiveness, marked by increased EMT signaling and complement activity. We identify distinct epithelial gene signatures for PPx and GPx that can accurately classify diagnostic samples and likely inform therapy.
First Page
1
Last Page
20
PubMed ID
41481418
Volume
45
Issue
1
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
Recommended Citation
Mukund, Kavitha; Veraksa, Darya; Frankhouser, David; Yang, Lixin; Tomsic, Jerneja; Pillai, Raju; Atti, Srijan; Mesrizadeh, Zahra; Schmolze, Daniel; Zabaleta, Jovanny; Wu, Xiao-Cheng; LeBlanc, Mary-Anne; Miele, Lucio; Ochoa, Augusto; Seewaldt, Victoria; and Subramaniam, Shankar, "Spatially distinct cellular and molecular landscapes define prognosis in triple-negative breast cancer" (2026). School of Medicine Faculty Publications. 4420.
https://digitalscholar.lsuhsc.edu/som_facpubs/4420
10.1016/j.celrep.2025.116752