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Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes

Author

Listed:
  • Karama Asleh

    (University of British Columbia
    University of British Columbia)

  • Gian Luca Negri

    (University of British Columbia)

  • Sandra E. Spencer Miko

    (University of British Columbia)

  • Shane Colborne

    (University of British Columbia)

  • Christopher S. Hughes

    (University of British Columbia)

  • Xiu Q. Wang

    (University of British Columbia)

  • Dongxia Gao

    (University of British Columbia)

  • C. Blake Gilks

    (University of British Columbia
    University of British Columbia)

  • Stephen K. L. Chia

    (University of British Columbia)

  • Torsten O. Nielsen

    (University of British Columbia
    University of British Columbia)

  • Gregg B. Morin

    (University of British Columbia
    University of British Columbia)

Abstract

Despite advances in genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein level information. Formalin-fixed paraffin-embedded (FFPE) tissue specimens with extended clinical outcomes are widely available. Here, we perform comprehensive proteomic profiling of 300 FFPE breast cancer surgical specimens, 75 of each PAM50 subtype, from patients diagnosed in 2008-2013 (n = 178) and 1986-1992 (n = 122) with linked clinical outcomes. These two cohorts are analyzed separately, and we quantify 4214 proteins across all 300 samples. Within the aggressive PAM50-classified basal-like cases, proteomic profiling reveals two groups with one having characteristic immune hot expression features and highly favorable survival. Her2-Enriched cases separate into heterogeneous groups differing by extracellular matrix, lipid metabolism, and immune-response features. Within 88 triple-negative breast cancers, four proteomic clusters display features of basal-immune hot, basal-immune cold, mesenchymal, and luminal with disparate survival outcomes. Our proteomic analysis characterizes the heterogeneity of breast cancer in a clinically-applicable manner, identifies potential biomarkers and therapeutic targets, and provides a resource for clinical breast cancer classification.

Suggested Citation

  • Karama Asleh & Gian Luca Negri & Sandra E. Spencer Miko & Shane Colborne & Christopher S. Hughes & Xiu Q. Wang & Dongxia Gao & C. Blake Gilks & Stephen K. L. Chia & Torsten O. Nielsen & Gregg B. Morin, 2022. "Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28524-0
    DOI: 10.1038/s41467-022-28524-0
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    1. Jiawei Zhou & Amber Cipriani & Yutong Liu & Gang Fang & Quefeng Li & Yanguang Cao, 2023. "Mapping lesion-specific response and progression dynamics and inter-organ variability in metastatic colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Silje Kjølle & Kenneth Finne & Even Birkeland & Vandana Ardawatia & Ingeborg Winge & Sura Aziz & Gøril Knutsvik & Elisabeth Wik & Joao A. Paulo & Heidrun Vethe & Dimitrios Kleftogiannis & Lars A. Aksl, 2023. "Hypoxia induced responses are reflected in the stromal proteome of breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. 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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