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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Akbani, Rehan 
Ng, Patrick Kwok Shing 
Werner, Henrica MJ 
Shahmoradgoli, Maria 
Zhang, Fan 

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.

Description

Keywords

Cluster Analysis, Gene Dosage, Genome, Human, Humans, Neoplasm Proteins, Neoplasms, Organ Specificity, Proteomics, RNA, Messenger, Receptor, ErbB-2, Signal Transduction, Statistics, Nonparametric

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
MRC (unknown)