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

Sabra I. Djomehri, Maria E. Gonzalez, Felipe da Veiga Leprevost, Shilpa R. Tekula, Hui-Yin Chang, Marissa J. White, Ashley Cimino-Mathews, Boris Burman, Venkatesha Basrur, Pedram Argani, Alexey I. Nesvizhskii () and Celina G. Kleer ()
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Sabra I. Djomehri: University of Michigan Medical School
Maria E. Gonzalez: University of Michigan Medical School
Felipe da Veiga Leprevost: University of Michigan Medical School
Shilpa R. Tekula: University of Michigan Medical School
Hui-Yin Chang: University of Michigan Medical School
Marissa J. White: Johns Hopkins University
Ashley Cimino-Mathews: Johns Hopkins University
Boris Burman: University of Michigan Medical School
Venkatesha Basrur: University of Michigan Medical School
Pedram Argani: Johns Hopkins University
Alexey I. Nesvizhskii: University of Michigan Medical School
Celina G. Kleer: University of Michigan Medical School

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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 increases related to epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways. MBC subtypes exhibit distinct upregulated profiles, including translation and ribosomal events in spindle, inflammation- and apical junction-related proteins in squamous, and extracellular matrix proteins in sarcomatoid subtypes. Comparison of the proteomes of human spindle MBC with mouse spindle (CCN6 knockout) MBC tumors reveals a shared spindle-specific signature of 17 upregulated proteins involved in translation and 19 downregulated proteins with roles in cell metabolism. These data identify potential subtype specific MBC biomarkers and therapeutic targets.

Date: 2020
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DOI: 10.1038/s41467-020-15283-z

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