title: A pan-cancer proteomic perspective on The Cancer Genome Atlas.
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.
authors.affiliation: 1] Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2].
authors.forename: Rehan
authors.initials: R
authors.lastname: Akbani
authors.affiliation: 1] Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA [2].
authors.forename: Patrick Kwok Shing
authors.initials: PK
authors.lastname: Ng
authors.affiliation: 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].
authors.forename: Henrica M J
authors.initials: HM
authors.lastname: Werner
authors.affiliation: Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Shahmoradgoli
authors.affiliation: Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Ju
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yoshihara
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Ling
authors.affiliation: Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Elena G
authors.initials: EG
authors.lastname: Seviour
authors.affiliation: Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Prahlad T
authors.initials: PT
authors.lastname: Ram
authors.affiliation: Hamon Center for Therapeutic Oncology, Internal Medicine, Pharmacology, 1801 Inwood Rd, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Tong
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Medical Research Council Biostatistics Unit, Cambridge CB2 0SR, UK.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hill
authors.affiliation: Medical Research Council Biostatistics Unit, Cambridge CB2 0SR, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Dondelinger
authors.affiliation: 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.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Städler
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Byers
authors.affiliation: Department of Surgical Oncology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: 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.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Broom
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Roeland G W
authors.initials: RG
authors.lastname: Verhaak
authors.affiliation: Department of Bioinformatics and Computational Biology, 1400 Pressler St., The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Sach
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Systems Biology, 1515 Holcombe Blvd, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D016000:Cluster Analysis; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D018709:Statistics, Nonparametric
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human