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Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers

Author

Listed:
  • Fengju Chen

    (Baylor College of Medicine)

  • Darshan S. Chandrashekar

    (University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Sooryanarayana Varambally

    (University of Alabama at Birmingham
    University of Alabama at Birmingham
    University of Alabama at Birmingham)

  • Chad J. Creighton

    (Baylor College of Medicine
    The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine
    Baylor College of Medicine)

Abstract

Mass-spectrometry-based proteomic profiling of human cancers has the potential for pan-cancer analyses to identify molecular subtypes and associated pathway features that might be otherwise missed using transcriptomics. Here, we classify 532 cancers, representing six tissue-based types (breast, colon, ovarian, renal, uterine), into ten proteome-based, pan-cancer subtypes that cut across tumor lineages. The proteome-based subtypes are observable in external cancer proteomic datasets surveyed. Gene signatures of oncogenic or metabolic pathways can further distinguish between the subtypes. Two distinct subtypes both involve the immune system, one associated with the adaptive immune response and T-cell activation, and the other associated with the humoral immune response. Two additional subtypes each involve the tumor stroma, one of these including the collagen VI interacting network. Three additional proteome-based subtypes—respectively involving proteins related to Golgi apparatus, hemoglobin complex, and endoplasmic reticulum—were not reflected in previous transcriptomics analyses. A data portal is available at UALCAN website.

Suggested Citation

  • Fengju Chen & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2019. "Pan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13528-0
    DOI: 10.1038/s41467-019-13528-0
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    Cited by:

    1. Yiqun Zhang & Fengju Chen & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2022. "Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Fengju Chen & Yiqun Zhang & Darshan S. Chandrashekar & Sooryanarayana Varambally & Chad J. Creighton, 2023. "Global impact of somatic structural variation on the cancer proteome," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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