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

Silje Kjølle, Kenneth Finne, Even Birkeland, Vandana Ardawatia, Ingeborg Winge, Sura Aziz, Gøril Knutsvik, Elisabeth Wik, Joao A. Paulo, Heidrun Vethe, Dimitrios Kleftogiannis and Lars A. Akslen ()
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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
Gøril Knutsvik: University of Bergen
Elisabeth Wik: University of Bergen
Joao A. Paulo: Harvard Medical School
Heidrun Vethe: University of Bergen
Dimitrios Kleftogiannis: University of Bergen
Lars A. Akslen: University of Bergen

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39287-7

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