IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29444-9.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29444-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-29444-9?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. Fredrik Edfors & Andreas Hober & Klas Linderbäck & Gianluca Maddalo & Alireza Azimi & Åsa Sivertsson & Hanna Tegel & Sophia Hober & Cristina Al-Khalili Szigyarto & Linn Fagerberg & Kalle Feilitzen & P, 2018. "Enhanced validation of antibodies for research applications," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. 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.
    3. Lei Li & Yuhong Wei & Christine To & Chang-Qi Zhu & Jiefei Tong & Nhu-An Pham & Paul Taylor & Vladimir Ignatchenko & Alex Ignatchenko & Wen Zhang & Dennis Wang & Naoki Yanagawa & Ming Li & Melania Pin, 2014. "Integrated Omic analysis of lung cancer reveals metabolism proteome signatures with prognostic impact," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    4. Paul A. Stewart & Eric A. Welsh & Robbert J. C. Slebos & Bin Fang & Victoria Izumi & Matthew Chambers & Guolin Zhang & Ling Cen & Fredrik Pettersson & Yonghong Zhang & Zhihua Chen & Chia-Ho Cheng & Ra, 2019. "Proteogenomic landscape of squamous cell lung cancer," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    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. Kyu Jin Song & Seunghyuk Choi & Kwoneel Kim & Hee Sang Hwang & Eunhyong Chang & Ji Soo Park & Seok Bo Shim & Seunghwan Choi & Yong Jin Heo & Woo Ju An & Dae Yeol Yang & Kyung-Cho Cho & Wonjun Ji & Cha, 2024. "Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    2. Gaopeng Hou & Wandy Beatty & Lili Ren & Yaw Shin Ooi & Juhee Son & Yinxing Zhu & Qingyu Sheng & Wanyi Huang & Dian Li & Constin Liu & Olivia L. Welsh & Danica M. Sutherland & Terence S. Dermody & Chen, 2025. "SAMD9 senses cytosolic double-stranded nucleic acids in epithelial and mesenchymal cells to induce antiviral immunity," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    3. Natalia Pardo-Lorente & Anestis Gkanogiannis & Luca Cozzuto & Antoni Gañez Zapater & Lorena Espinar & Ritobrata Ghose & Jacqueline Severino & Laura García-López & Rabia Gül Aydin & Laura Martin & Mari, 2024. "Nuclear localization of MTHFD2 is required for correct mitosis progression," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    4. 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.
    5. Manish Kumar & David Molkentine & Jessica Molkentine & Kathleen Bridges & Tongxin Xie & Liangpeng Yang & Andrew Hefner & Meng Gao & Reshub Bahri & Annika Dhawan & Mitchell J. Frederick & Sahil Seth & , 2021. "Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    6. Feng Wang & Yang Xu & Robert Wang & Beatrice Zhang & Noah Smith & Amber Notaro & Samantha Gaerlan & Eric Kutschera & Kathryn E. Kadash-Edmondson & Yi Xing & Lan Lin, 2023. "TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Isabelle Rose Leo & Elena Kunold & Anastasia Audrey & Marianna Tampere & Jürgen Eirich & Janne Lehtiö & Rozbeh Jafari, 2025. "Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    9. Christopher Tosh & Mauricio Tec & Jessica B. White & Jeffrey F. Quinn & Glorymar Ibanez Sanchez & Paul Calder & Andrew L. Kung & Filemon S. Dela Cruz & Wesley Tansey, 2025. "A Bayesian active learning platform for scalable combination drug screens," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    10. Miquel Anglada-Girotto & Ludovica Ciampi & Sophie Bonnal & Sarah A. Head & Samuel Miravet-Verde & Luis Serrano, 2024. "In silico RNA isoform screening to identify potential cancer driver exons with therapeutic applications," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    11. Yongqiang Zheng & Kai Yu & Jin-Fei Lin & Zhuoran Liang & Qingfeng Zhang & Junteng Li & Qi-Nian Wu & Cai-Yun He & Mei Lin & Qi Zhao & Zhi-Xiang Zuo & Huai-Qiang Ju & Rui-Hua Xu & Ze-Xian Liu, 2025. "Deep learning prioritizes cancer mutations that alter protein nucleocytoplasmic shuttling to drive tumorigenesis," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    12. Joshua D. Spitzberg & Scott Ferguson & Katherine S. Yang & Hannah M. Peterson & Jonathan C. T. Carlson & Ralph Weissleder, 2023. "Multiplexed analysis of EV reveals specific biomarker composition with diagnostic impact," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Julia Ogden & Robert Sellers & Sudhakar Sahoo & Anthony Oojageer & Anshuman Chaturvedi & Caroline Dive & Carlos Lopez-Garcia, 2025. "A human model to deconvolve genotype-phenotype causations in lung squamous cell carcinoma," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    14. Fei Li & Yizhe Wang & Inah Hwang & Ja-Young Jang & Libo Xu & Zhong Deng & Eun Young Yu & Yiming Cai & Caizhi Wu & Zhenbo Han & Yu-Han Huang & Xiangao Huang & Ling Zhang & Jun Yao & Neal F. Lue & Paul , 2023. "Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    15. Dohoon Lee & Bonil Koo & Seokhyeon Kim & Jamin Byun & Junshik Hong & Dong-Yeop Shin & Choong-Hyun Sun & Jaesung Kim & Ji-Joon Song & Siddhartha Jaiswal & Sung-Soo Yoon & Sun Kim & Youngil Koh, 2025. "Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    16. Veronica Rendo & Michael Schubert & Nicholas Khuu & Maria F. Suarez Peredo Rodriguez & Declan Whyte & Xiao Ling & Anouk Brink & Kaimeng Huang & Michelle Swift & Yizhou He & Johanna Zerbib & Ross Smith, 2025. "A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    17. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    18. Paul A Stewart & Katja Parapatics & Eric A Welsh & André C Müller & Haoyun Cao & Bin Fang & John M Koomen & Steven A Eschrich & Keiryn L Bennett & Eric B Haura, 2015. "A Pilot Proteogenomic Study with Data Integration Identifies MCT1 and GLUT1 as Prognostic Markers in Lung Adenocarcinoma," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-18, November.
    19. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    20. 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.

    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_s41467-022-29444-9. 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.