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

Author

Listed:
  • Sabra I. Djomehri

    (University of Michigan Medical School
    University of Michigan
    University of Michigan)

  • Maria E. Gonzalez

    (University of Michigan Medical School
    University of Michigan)

  • Felipe da Veiga Leprevost

    (University of Michigan Medical School)

  • Shilpa R. Tekula

    (University of Michigan Medical School
    University of Michigan)

  • 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
    University of Michigan)

  • Venkatesha Basrur

    (University of Michigan Medical School)

  • Pedram Argani

    (Johns Hopkins University)

  • Alexey I. Nesvizhskii

    (University of Michigan Medical School
    University of Michigan)

  • Celina G. Kleer

    (University of Michigan Medical School
    University of Michigan)

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.

Suggested Citation

  • 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 & Ale, 2020. "Quantitative proteomic landscape of metaplastic breast carcinoma pathological subtypes and their relationship to triple-negative tumors," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15283-z
    DOI: 10.1038/s41467-020-15283-z
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    Cited by:

    1. Brijesh Kumar & Aditi S. Khatpe & Jiang Guanglong & Katie Batic & Poornima Bhat-Nakshatri & Maggie M. Granatir & Rebekah Joann Addison & Megan Szymanski & Lee Ann Baldridge & Constance J. Temm & Georg, 2023. "Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. James T. Topham & Erica S. Tsang & Joanna M. Karasinska & Andrew Metcalfe & Hassan Ali & Steve E. Kalloger & Veronika Csizmok & Laura M. Williamson & Emma Titmuss & Karina Nielsen & Gian Luca Negri & , 2022. "Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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