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Nat Commun. 2014 May 29;5:3887. doi: 10.1038/ncomms4887.

A pan-cancer proteomic perspective on The Cancer Genome Atlas.

Author information

1
1] Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2].
2
1] Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2].
3
1] Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, 5023 Bergen, Norway [3].
4
Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
5
Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
6
1] Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Applied Mathematics, Kumoh National Institute of Technology, Gumi 730-701, South Korea.
7
Hamon Center for Therapeutic Oncology, Internal Medicine, Pharmacology, 1801 Inwood Rd, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
8
Department of Thoracic/Head and Neck Medical Oncology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
9
Medical Research Council Biostatistics Unit, Cambridge CB2 0SR, UK.
10
1] Medical Research Council Biostatistics Unit, Cambridge CB2 0SR, UK [2] Department of Biochemistry, The Netherlands Cancer Institute, Postbox 90203, 1006 BE Amsterdam, The Netherlands.
11
Department of Surgical Oncology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
12
1] Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2] Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
13
1] Medical Research Council Biostatistics Unit, Cambridge CB2 0SR, UK [2] Cancer Research UK Cambridge Institute, School of Clinical Medicine, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.

Abstract

Protein levels and function are poorly predicted by genomic and transcriptomic analysis of patient tumours. Therefore, direct study of the functional proteome has the potential to provide a wealth of information that complements and extends genomic, epigenomic and transcriptomic analysis in The Cancer Genome Atlas (TCGA) projects. Here we use reverse-phase protein arrays to analyse 3,467 patient samples from 11 TCGA 'Pan-Cancer' diseases, using 181 high-quality antibodies that target 128 total proteins and 53 post-translationally modified proteins. The resultant proteomic data are integrated with genomic and transcriptomic analyses of the same samples to identify commonalities, differences, emergent pathways and network biology within and across tumour lineages. In addition, tissue-specific signals are reduced computationally to enhance biomarker and target discovery spanning multiple tumour lineages. This integrative analysis, with an emphasis on pathways and potentially actionable proteins, provides a framework for determining the prognostic, predictive and therapeutic relevance of the functional proteome.

PMID:
24871328
PMCID:
PMC4109726
DOI:
10.1038/ncomms4887
[Indexed for MEDLINE]
Free PMC Article
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