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

TitlePan-cancer molecular subtypes revealed by mass-spectrometry-based proteomic characterization of more than 500 human cancers.
Publication TypeJournal Article
Year of Publication2019
AuthorsChen, F, Chandrashekar, DS, Varambally, S, Creighton, CJ
JournalNat Commun
Volume10
Issue1
Pagination5679
Date Published2019 Dec 12
ISSN2041-1723
KeywordsAdaptive Immunity, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Humans, Mass Spectrometry, Metabolic Networks and Pathways, Neoplasm Proteins, Neoplasms, Proteomics, Transcriptome
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.

DOI10.1038/s41467-019-13528-0
Alternate JournalNat Commun
PubMed ID31831737
PubMed Central IDPMC6908580
Grant ListCA125123 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
CA125123 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /

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