Document Type
Article
Publication Date
1-29-2026
Original Citation
Foroughi Pour A,
Wu T,
Noorbakhsh J,
Martinek J,
Sivajothi S,
Robson P,
Palucka K,
Chuang J.
Prediction of outcome from spatial Protein profiling of triple-negative breast cancers. Commun Med (Lond). 2026;6(1).
Keywords
JGM
JAX Source
Commun Med (Lond). 2026;6(1).
ISSN
2730-664X
PMID
41611876
DOI
https://doi.org/10.1038/s43856-026-01400-4
Grant
Research reported in this publication was supported by NIH grant R01CA230031, NIH grant RO1CA219880, JAX Cancer Center NIH/NCI grant P30 CA034196, and Yale Cancer Center NIH/NCI grant P30 CA016359.
Abstract
BACKGROUND: In tumors, reciprocal spatial interactions between immune cells, their mediators, the extracellular matrix, and mutated neoplastic cells impact all aspects of treatment resistance. The operational mechanisms of these interactions are foundational for developing insights and targets for cancer therapy and prevention. Spatial quantification of the tumor microenvironment system from image data has untapped potential for patient stratification.
METHODS: Here, we present SparTile, a powerful computational approach for the analysis of multiplex proteomics images to reveal clinically relevant structural organization in the tumor microenvironment. SparTile enables robust and unbiased identification and characterization of tumor microenvironments based on spatial relationships among protein markers without the need for cell segmentation or classification.
RESULTS: Applied to tissues of patients with triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, SparTile identifies repeatable microenvironments with specific cellular relationships. Several microenvironments are characterized by risk markers such as Ki67+ (p-value = 0.052) and vimentin+ (p-value < 0.01) tumor cells, which correlate with poor survival. Furthermore, myeloid markers in an MX1-positive tumor environment correlate with shorter survival (p-value = 0.04). Finally, the relative distance between tumor and myeloid cell markers is a strong prognostic risk factor in multivariate Cox models (p-value < 0.01). This distance metric is externally validated on two datasets of breast cancer multiplex images (p-values < 0.01).
CONCLUSIONS: Our results show that unbiased protein-based and segmentation-free spatial analysis is effective for identifying clinically relevant biomarkers from multiplex tumor images and identifying predictive biology.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.