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Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes

Author

Listed:
  • Shideh Mirhadi

    (Program in Cell Biology, Hospital for Sick Children
    University of Toronto)

  • Shirley Tam

    (University Health Network)

  • Quan Li

    (University Health Network)

  • Nadeem Moghal

    (University Health Network)

  • Nhu-An Pham

    (University Health Network)

  • Jiefei Tong

    (Program in Cell Biology, Hospital for Sick Children)

  • Brian J. Golbourn

    (University of Pittsburgh School of Medicine)

  • Jonathan R. Krieger

    (SPARC BioCentre, Hospital for Sick Children)

  • Paul Taylor

    (Program in Cell Biology, Hospital for Sick Children)

  • Ming Li

    (University Health Network)

  • Jessica Weiss

    (Department of Biostatistics, Princess Margaret Cancer Centre)

  • Sebastiao N. Martins-Filho

    (University Health Network
    University of Toronto)

  • Vibha Raghavan

    (University Health Network)

  • Yasin Mamatjan

    (University Health Network)

  • Aafaque A. Khan

    (Program in Cell Biology, Hospital for Sick Children)

  • Michael Cabanero

    (University Health Network
    University of Toronto)

  • Shingo Sakashita

    (University Health Network)

  • Kugeng Huo

    (University Health Network)

  • Sameer Agnihotri

    (University of Pittsburgh School of Medicine)

  • Kota Ishizawa

    (University Health Network)

  • Thomas K. Waddell

    (University Health Network
    University of Toronto)

  • Gelareh Zadeh

    (University Health Network
    University of Toronto)

  • Kazuhiro Yasufuku

    (University Health Network
    University of Toronto)

  • Geoffrey Liu

    (University Health Network
    University of Toronto
    University of Toronto)

  • Frances A. Shepherd

    (University Health Network
    University of Toronto)

  • Michael F. Moran

    (Program in Cell Biology, Hospital for Sick Children
    University of Toronto
    University Health Network)

  • Ming-Sound Tsao

    (University Health Network
    University of Toronto
    University of Toronto)

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. Only a fraction of NSCLC harbor actionable driver mutations and there is an urgent need for patient-derived model systems that will enable the development of new targeted therapies. NSCLC and other cancers display profound proteome remodeling compared to normal tissue that is not predicted by DNA or RNA analyses. Here, we generate 137 NSCLC patient-derived xenografts (PDXs) that recapitulate the histology and molecular features of primary NSCLC. Proteome analysis of the PDX models reveals 3 adenocarcinoma and 2 squamous cell carcinoma proteotypes that are associated with different patient outcomes, protein-phosphotyrosine profiles, signatures of activated pathways and candidate targets, and in adenocarcinoma, stromal immune features. These findings portend proteome-based NSCLC classification and treatment and support the PDX resource as a viable model for the development of new targeted therapies.

Suggested Citation

  • Shideh Mirhadi & Shirley Tam & Quan Li & Nadeem Moghal & Nhu-An Pham & Jiefei Tong & Brian J. Golbourn & Jonathan R. Krieger & Paul Taylor & Ming Li & Jessica Weiss & Sebastiao N. Martins-Filho & Vibh, 2022. "Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29444-9
    DOI: 10.1038/s41467-022-29444-9
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