A pan-cancer proteomic perspective on The Cancer Genome Atlas

被引：416

作者：

Akbani, Rehan ^{[1
]}

Ng, Patrick Kwok Shing ^{[2
]}

Werner, Henrica M. J. ^{[2
,3
]}

Shahmoradgoli, Maria ^{[2
]}

Zhang, Fan ^{[2
]}

Ju, Zhenlin ^{[1
]}

Liu, Wenbin ^{[1
]}

Yang, Ji-Yeon ^{[1
,4
]}

Yoshihara, Kosuke ^{[1
]}

Li, Jun ^{[1
]}

Ling, Shiyun ^{[1
]}

Seviour, Elena G. ^{[2
]}

Ram, Prahlad T. ^{[2
]}

Minna, John D. ^{[5
]}

Diao, Lixia ^{[1
]}

Tong, Pan ^{[1
]}

Heymach, John V. ^{[6
]}

Hill, Steven M. ^{[7
]}

Dondelinger, Frank ^{[7
]}

Stadler, Nicolas ^{[7
,8
]}

Byers, Lauren A. ^{[6
]}

Meric-Bernstam, Funda ^{[9
]}

Weinstein, John N. ^{[1
,2
]}

Broom, Bradley M. ^{[1
]}

Verhaak, Roeland G. W. ^{[1
]}

Liang, Han ^{[1
]}

Mukherjee, Sach ^{[7
,10
]}

Lu, Yiling ^{[2
]}

Mills, Gordon B. ^{[2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA

[3] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, N-5023 Bergen, Norway

[4] Kumoh Natl Inst Technol, Dept Appl Math, Gumi 730701, South Korea

[5] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol, Dallas, TX 75235 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Thoracic Head & Neck Med Oncol, Houston, TX 77030 USA

[7] MRC, Biostat Unit, Cambridge CB2 0SR, England

[8] Netherlands Canc Inst, Dept Biochem, NL-1006 BE Amsterdam, Netherlands

[9] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA

[10] Univ Cambridge, Sch Clin Med, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

美国国家卫生研究院;

关键词：

SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; GENE AMPLIFICATION; PROTEIN EXPRESSION; MICROARRAY ANALYSIS; PATHWAY ACTIVATION; MESSENGER-RNA; COPY NUMBER; E-CADHERIN; HER2;

D O I：

10.1038/ncomms4887

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

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