System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis

The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures. [Display omitted] •Deep proteomic profiling of luminal breast cancer progression•Super-SILAC quantified over 10,000 proteins across a cohort of 88 clinical samples•Tumor cells exhibit higher protein turnover and metabolic remodeling•Proteomic profiles of primary tumors and lymph node metastases are highly similar Deep proteomic analysis of ER-positive clinical breast tumors points to key proteins and processes that are associated with tumorigenesis and metastatic spread.