Dataset Information

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): Orbitrap Fusion

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

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			Action	DRS
	PRF_F_2019_C_KLEE_147_47965_47974_1.pepXML	Pepxml
	PRF_F_2019_C_KLEE_147_47965_47974_1.raw	Raw
	PRF_F_2019_C_KLEE_147_47965_47974_2.pepXML	Pepxml
	PRF_F_2019_C_KLEE_147_47965_47974_2.raw	Raw
	PRF_F_2019_C_KLEE_147_47965_47974_3.pepXML	Pepxml

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

Djomehri Sabra I SI Gonzalez Maria E ME da Veiga Leprevost Felipe F Tekula Shilpa R SR Chang Hui-Yin HY White Marissa J MJ Cimino-Mathews Ashley A Burman Boris B Basrur Venkatesha V Argani Pedram P Nesvizhskii Alexey I AI Kleer Celina G CG

Nature communications 20200407 1

Metaplastic breast carcinoma (MBC) is a highly 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 quantify 5798 proteins in MBC, TNBC, and normal breast from 27 patients. Comparing MBC and TNBC protein profiles we show MBC-specific in ...[more]

PMID: 32265444

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