IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28524-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28524-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28524-0?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. Henrik J. Johansson & Fabio Socciarelli & Nathaniel M. Vacanti & Mads H. Haugen & Yafeng Zhu & Ioannis Siavelis & Alejandro Fernandez-Woodbridge & Miriam R. Aure & Bengt Sennblad & Mattias Vesterlund , 2019. "Breast cancer quantitative proteome and proteogenomic landscape," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    3. Sohrab P. Shah & Andrew Roth & Rodrigo Goya & Arusha Oloumi & Gavin Ha & Yongjun Zhao & Gulisa Turashvili & Jiarui Ding & Kane Tse & Gholamreza Haffari & Ali Bashashati & Leah M. Prentice & Jaswinder , 2012. "The clonal and mutational evolution spectrum of primary triple-negative breast cancers," Nature, Nature, vol. 486(7403), pages 395-399, June.
    4. 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.
    5. Philipp Mertins & D. R. Mani & Kelly V. Ruggles & Michael A. Gillette & Karl R. Clauser & Pei Wang & Xianlong Wang & Jana W. Qiao & Song Cao & Francesca Petralia & Emily Kawaler & Filip Mundt & Karste, 2016. "Proteogenomics connects somatic mutations to signalling in breast cancer," Nature, Nature, vol. 534(7605), pages 55-62, June.
    6. Kuan-lin Huang & Shunqiang Li & Philipp Mertins & Song Cao & Harsha P. Gunawardena & Kelly V. Ruggles & D. R. Mani & Karl R. Clauser & Maki Tanioka & Jerry Usary & Shyam M. Kavuri & Ling Xie & Christo, 2017. "Proteogenomic integration reveals therapeutic targets in breast cancer xenografts," Nature Communications, Nature, vol. 8(1), pages 1-17, April.
    7. Shankha Satpathy & Eric J. Jaehnig & Karsten Krug & Beom-Jun Kim & Alexander B. Saltzman & Doug W. Chan & Kimberly R. Holloway & Meenakshi Anurag & Chen Huang & Purba Singh & Ari Gao & Noel Namai & Yo, 2020. "Microscaled proteogenomic methods for precision oncology," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    8. Kuan-lin Huang & Shunqiang Li & Philipp Mertins & Song Cao & Harsha P. Gunawardena & Kelly V. Ruggles & D. R. Mani & Karl R. Clauser & Maki Tanioka & Jerry Usary & Shyam M. Kavuri & Ling Xie & Christo, 2017. "Correction: Corrigendum: Proteogenomic integration reveals therapeutic targets in breast cancer xenografts," Nature Communications, Nature, vol. 8(1), pages 1-1, April.
    9. Philip J. Stephens & Patrick S. Tarpey & Helen Davies & Peter Van Loo & Chris Greenman & David C. Wedge & Serena Nik-Zainal & Sancha Martin & Ignacio Varela & Graham R. Bignell & Lucy R. Yates & Elli , 2012. "The landscape of cancer genes and mutational processes in breast cancer," Nature, Nature, vol. 486(7403), pages 400-404, June.
    10. Mathias Kalxdorf & Torsten Müller & Oliver Stegle & Jeroen Krijgsveld, 2021. "IceR improves proteome coverage and data completeness in global and single-cell proteomics," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    11. Stefka Tyanova & Reidar Albrechtsen & Pauliina Kronqvist & Juergen Cox & Matthias Mann & Tamar Geiger, 2016. "Proteomic maps of breast cancer subtypes," Nature Communications, Nature, vol. 7(1), pages 1-11, April.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    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. S. Mouron & M. J. Bueno & A. Lluch & L. Manso & I. Calvo & J. Cortes & J. A. Garcia-Saenz & M. Gil-Gil & N. Martinez-Janez & J. V. Apala & E. Caleiras & Pilar Ximénez-Embún & J. Muñoz & L. Gonzalez-Co, 2022. "Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Sam Crowl & Ben T. Jordan & Hamza Ahmed & Cynthia X. Ma & Kristen M. Naegle, 2022. "KSTAR: An algorithm to predict patient-specific kinase activities from phosphoproteomic data," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Jennifer G. Abelin & Erik J. Bergstrom & Keith D. Rivera & Hannah B. Taylor & Susan Klaeger & Charles Xu & Eva K. Verzani & C. Jackson White & Hilina B. Woldemichael & Maya Virshup & Meagan E. Olive &, 2023. "Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Brian D. Lehmann & Antonio Colaprico & Tiago C. Silva & Jianjiao Chen & Hanbing An & Yuguang Ban & Hanchen Huang & Lily Wang & Jamaal L. James & Justin M. Balko & Paula I. Gonzalez-Ericsson & Melinda , 2021. "Multi-omics analysis identifies therapeutic vulnerabilities in triple-negative breast cancer subtypes," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    5. 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.
    6. 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.
    7. Zaili Luo & Dazhuan Xin & Yunfei Liao & Kalen Berry & Sean Ogurek & Feng Zhang & Liguo Zhang & Chuntao Zhao & Rohit Rao & Xinran Dong & Hao Li & Jianzhong Yu & Yifeng Lin & Guoying Huang & Lingli Xu &, 2023. "Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. 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.
    9. Yuen Lam Dora Ng & Evelyn Ramberger & Stephan R. Bohl & Anna Dolnik & Christian Steinebach & Theresia Conrad & Sina Müller & Oliver Popp & Miriam Kull & Mohamed Haji & Michael Gütschow & Hartmut Döhne, 2022. "Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
    14. Yuanyuan Qu & Jinwen Feng & Xiaohui Wu & Lin Bai & Wenhao Xu & Lingli Zhu & Yang Liu & Fujiang Xu & Xuan Zhang & Guojian Yang & Jiacheng Lv & Xiuping Chen & Guo-Hai Shi & Hong-Kai Wang & Da-Long Cao &, 2022. "A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    15. Isabelle Rose Leo & Luay Aswad & Matthias Stahl & Elena Kunold & Frederik Post & Tom Erkers & Nona Struyf & Georgios Mermelekas & Rubin Narayan Joshi & Eva Gracia-Villacampa & Päivi Östling & Olli P. , 2022. "Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. 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).
    17. 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.
    18. 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.
    19. 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.
    20. 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.

    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:13:y:2022:i:1:d:10.1038_s41467-022-28524-0. 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.