IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39287-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39287-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39287-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Charles M. Perou & Therese Sørlie & Michael B. Eisen & Matt van de Rijn & Stefanie S. Jeffrey & Christian A. Rees & Jonathan R. Pollack & Douglas T. Ross & Hilde Johnsen & Lars A. Akslen & Øystein Flu, 2000. "Molecular portraits of human breast tumours," Nature, Nature, vol. 406(6797), pages 747-752, August.
    2. Gøril Knutsvik & Ingunn M Stefansson & Sura Aziz & Jarle Arnes & Johan Eide & Karin Collett & Lars A Akslen, 2014. "Evaluation of Ki67 Expression across Distinct Categories of Breast Cancer Specimens: A Population-Based Study of Matched Surgical Specimens, Core Needle Biopsies and Tissue Microarrays," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-11, November.
    3. Peter Carmeliet & Rakesh K. Jain, 2011. "Molecular mechanisms and clinical applications of angiogenesis," Nature, Nature, vol. 473(7347), pages 298-307, May.
    4. Inês Godet & Yu Jung Shin & Julia A. Ju & I Chae Ye & Guannan Wang & Daniele M. Gilkes, 2019. "Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    5. Kui Shen & Nan Song & Youngchul Kim & Chunqiao Tian & Shara D Rice & Michael J Gabrin & W Fraser Symmans & Lajos Pusztai & Jae K Lee, 2012. "A Systematic Evaluation of Multi-Gene Predictors for the Pathological Response of Breast Cancer Patients to Chemotherapy," PLOS ONE, Public Library of Science, vol. 7(11), pages 1-9, November.
    6. Christina Curtis & Sohrab P. Shah & Suet-Feung Chin & Gulisa Turashvili & Oscar M. Rueda & Mark J. Dunning & Doug Speed & Andy G. Lynch & Shamith Samarajiwa & Yinyin Yuan & Stefan Gräf & Gavin Ha & Gh, 2012. "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups," Nature, Nature, vol. 486(7403), pages 346-352, June.
    7. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
    8. 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.
    9. Thomas R. Cox & Robin M. H. Rumney & Erwin M. Schoof & Lara Perryman & Anette M. Høye & Ankita Agrawal & Demelza Bird & Norain Ab Latif & Hamish Forrest & Holly R. Evans & Iain D. Huggins & Georgina L, 2015. "RETRACTED ARTICLE: The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase," Nature, Nature, vol. 522(7554), pages 106-110, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Peter Eirew & Ciara O’Flanagan & Jerome Ting & Sohrab Salehi & Jazmine Brimhall & Beixi Wang & Justina Biele & Teresa Algara & So Ra Lee & Corey Hoang & Damian Yap & Steven McKinney & Cherie Bates & E, 2022. "Accurate determination of CRISPR-mediated gene fitness in transplantable tumours," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Sandra M. Rocha & Sílvia Socorro & Luís A. Passarinha & Cláudio J. Maia, 2022. "Comprehensive Landscape of STEAP Family Members Expression in Human Cancers: Unraveling the Potential Usefulness in Clinical Practice Using Integrated Bioinformatics Analysis," Data, MDPI, vol. 7(5), pages 1-48, May.
    3. M. G. Filippone & D. Gaglio & R. Bonfanti & F. A. Tucci & E. Ceccacci & R. Pennisi & M. Bonanomi & G. Jodice & M. Tillhon & F. Montani & G. Bertalot & S. Freddi & M. Vecchi & A. Taglialatela & M. Roma, 2022. "CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Zheqi Li & Olivia McGinn & Yang Wu & Amir Bahreini & Nolan M. Priedigkeit & Kai Ding & Sayali Onkar & Caleb Lampenfeld & Carol A. Sartorius & Lori Miller & Margaret Rosenzweig & Ofir Cohen & Nikhil Wa, 2022. "ESR1 mutant breast cancers show elevated basal cytokeratins and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    6. 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.
    7. Lingsong Meng & Dorina Avram & George Tseng & Zhiguang Huo, 2022. "Outcome‐guided sparse K‐means for disease subtype discovery via integrating phenotypic data with high‐dimensional transcriptomic data," Journal of the Royal Statistical Society Series C, Royal Statistical Society, vol. 71(2), pages 352-375, March.
    8. Yang, Xi & Hoadley, Katherine A. & Hannig, Jan & Marron, J.S., 2023. "Jackstraw inference for AJIVE data integration," Computational Statistics & Data Analysis, Elsevier, vol. 180(C).
    9. Aleix Prat & Fara Brasó-Maristany & Olga Martínez-Sáez & Esther Sanfeliu & Youli Xia & Meritxell Bellet & Patricia Galván & Débora Martínez & Tomás Pascual & Mercedes Marín-Aguilera & Anna Rodríguez &, 2023. "Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Manish G & Anil Kumar Badana & Rama Rao Malla, 2017. "Emerging Diagnostic and Prognostic Biomarkers of Triple Negative Breast Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 1(3), pages 561-565, August.
    11. Jacob Elnaggar & Fern Tsien & Lucio Miele & Chindo Hicks & Clayton Yates & Melisa Davis, 2019. "An Integrative Genomics Approach for Associating Genetic Susceptibility with the Tumor Immune Microenvironment in Triple Negative Breast Cancer," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 15(1), pages 1-12, February.
    12. María Elena Martínez & Jonathan T Unkart & Li Tao & Candyce H Kroenke & Richard Schwab & Ian Komenaka & Scarlett Lin Gomez, 2017. "Prognostic significance of marital status in breast cancer survival: A population-based study," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-14, May.
    13. Yishai Shimoni, 2018. "Association between expression of random gene sets and survival is evident in multiple cancer types and may be explained by sub-classification," PLOS Computational Biology, Public Library of Science, vol. 14(2), pages 1-15, February.
    14. Marcin Pilarczyk & Mehdi Fazel-Najafabadi & Michal Kouril & Behrouz Shamsaei & Juozas Vasiliauskas & Wen Niu & Naim Mahi & Lixia Zhang & Nicholas A. Clark & Yan Ren & Shana White & Rashid Karim & Huan, 2022. "Connecting omics signatures and revealing biological mechanisms with iLINCS," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    15. Balkrishna Chaube & Kathryn M. Citrin & Mahnaz Sahraei & Abhishek K. Singh & Diego Saenz Urturi & Wen Ding & Richard W. Pierce & Raaisa Raaisa & Rebecca Cardone & Richard Kibbey & Carlos Fernández-Her, 2023. "Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    16. Zongchao Sun & Likun Yang & Abdukahar Kiram & Jing Yang & Zhuangzhuang Yang & Liwei Xiao & Yujing Yin & Jing Liu & Yan Mao & Danxia Zhou & Hao Yu & Zheng Zhou & Dengqiu Xu & Yuhuan Jia & Chenyun Ding , 2023. "FNIP1 abrogation promotes functional revascularization of ischemic skeletal muscle by driving macrophage recruitment," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Hugh Chen & Scott M. Lundberg & Su-In Lee, 2022. "Explaining a series of models by propagating Shapley values," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    18. Junhee Seok & Ronald W Davis & Wenzhong Xiao, 2015. "A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-15, May.
    19. Qing Qu & Yan Mao & Xiao-chun Fei & Kun-wei Shen, 2013. "The Impact of Androgen Receptor Expression on Breast Cancer Survival: A Retrospective Study and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-1, December.
    20. Nadege Gitego & Bogos Agianian & Oi Wei Mak & Vasantha Kumar MV & Emily H. Cheng & Evripidis Gavathiotis, 2023. "Chemical modulation of cytosolic BAX homodimer potentiates BAX activation and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39287-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.