Proteomic landscape of multi-layered breast cancer internal tumor heterogeneity

ABSTRACT: Breast cancer often presents with a high degree of intratumor heterogeneity, resulting in therapy resistance and tumor relapse. Here, we investigated spatial intratumor heterogeneity by integrating histopathological analyses and mass spectrometry-based proteomics. Using multilayered heterogeneity scoring, we identified the proteomic determinants of tumor heterogeneity and associated them with clinical and functional tumor characteristics. We found that molecular subtypes present lower heterogeneity with higher tumor grade, and demonstrate distinct subtype-specific profiles. However, even homogeneous tumors present high degrees of proteomic diversity, associated with proliferative and immune processes. Interestingly, tumor regions from molecularly-heterogeneous tumors, irrespective of their molecular subtype showed high proteomic similarity with enriched glutathione metabolism and proline biosynthesis pathways. Taken together the proteomic analyses revealed the association of internal tumor heterogeneity with cancer progression and immune selection, which can serve as a platform to decipher mechanisms underlying cancer evolution and therapy resistance.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Breast

DISEASE(S): Breast Cancer

SUBMITTER: Tamar Geiger  

LAB HEAD: Tamar Geiger

PROVIDER: PXD024190 | Pride | 2025-08-10

REPOSITORIES: Pride