Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness

0574522 - BFÚ 2024 RIV US eng J - Journal Article
Kvokačková, Barbora - Fedr, Radek - Kužílková, D. - Stuchlý, J. - Vávrová, A. - Navrátil, J. - Fabián, P. - Ondrussek, R. - Ovesná, P. - Remsik, J. - Bouchal, J. - Kalina, T. - Souček, Karel
Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness.
Molecular Oncology. Roč. 17, č. 6 (2023), s. 1024-1040. ISSN 1574-7891. E-ISSN 1878-0261
R&D Projects: GA MZd(CZ) NV18-08-00245; GA MZd(CZ) NU21-08-00023; GA ČR(CZ) GA20-22984S; GA ČR(CZ) GA21-11585S
Institutional support: RVO:68081707
Keywords : mass cytometry * phenotypic plasticity * single-cell profiles * triple-negative breast cancer * tumor heterogeneity * unsupervised machine learning algorithm
OECD category: Immunology
Impact factor: 6.6, year: 2022
Method of publishing: Open access
https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13365

Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.
Permanent Link: https://hdl.handle.net/11104/0350095