Quantitative proteomic landscape of metaplastic breast carcinoma pathological subtypes and their relationship to triple-negative tumors

ABSTRACT: Metaplastic breast carcinoma (MBC) is the most aggressive form of triple-negative cancer (TNBC), defined by the presence of “metaplastic” components of spindle, squamous, or sarcomatoid histology. The protein profiles underpinning the pathological subtypes and metastatic behavior of MBC are unknown. Using multiplex quantitative tandem mass tag-based proteomics we quantified 5,798 proteins in MBC, TNBC, and normal breast from 27 patients. MBC showed increased epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways compared to TNBC. MBC subtypes exhibited distinct upregulated profiles; translation and ribosomal events in spindle, inflammation and apical junctions in squamous, and extracellular matrix in sarcomatoid. Comparison of the proteomes of spindle MBC with MMTV-cre;Ccn6fl/fl spindle MBC tumors revealed a shared spindle-specific signature of 17 upregulated proteins involved in translation (e.g. RPL4,6,18, P3H1, PYCR1) and 19 downregulated proteins with roles in cell metabolism (e.g. ADH1B, ADH1C, LIPE, SOD1, FABP4). These data identify subtype specific MBC protein profiles providing biomarkers and therapeutic targets.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Mammary Gland

DISEASE(S): Breast Cancer

SUBMITTER: Sabra Djomehri  

LAB HEAD: Celina G. Kleer

PROVIDER: PXD014414 | Pride | 2020-04-22

REPOSITORIES: Pride