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Hypoxia induced responses are reflected in the stromal proteome of breast cancer

Author

Listed:
  • Silje Kjølle

    (University of Bergen)

  • Kenneth Finne

    (University of Bergen)

  • Even Birkeland

    (University of Bergen)

  • Vandana Ardawatia

    (University of Bergen)

  • Ingeborg Winge

    (University of Bergen)

  • Sura Aziz

    (University of Bergen
    Haukeland University Hospital)

  • Gøril Knutsvik

    (University of Bergen
    Haukeland University Hospital)

  • Elisabeth Wik

    (University of Bergen
    Haukeland University Hospital)

  • Joao A. Paulo

    (Harvard Medical School)

  • Heidrun Vethe

    (University of Bergen)

  • Dimitrios Kleftogiannis

    (University of Bergen
    University of Bergen)

  • Lars A. Akslen

    (University of Bergen
    Haukeland University Hospital)

Abstract

Cancers are often associated with hypoxia and metabolic reprogramming, resulting in enhanced tumor progression. Here, we aim to study breast cancer hypoxia responses, focusing on secreted proteins from low-grade (luminal-like) and high-grade (basal-like) cell lines before and after hypoxia. We examine the overlap between proteomics data from secretome analysis and laser microdissected human breast cancer stroma, and we identify a 33-protein stromal-based hypoxia profile (33P) capturing differences between luminal-like and basal-like tumors. The 33P signature is associated with metabolic differences and other adaptations following hypoxia. We observe that mRNA values for 33P predict patient survival independently of molecular subtypes and basic prognostic factors, also among low-grade luminal-like tumors. We find a significant prognostic interaction between 33P and radiation therapy.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39287-7
    DOI: 10.1038/s41467-023-39287-7
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