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Sci Rep. 2016 Oct 7;6:34949. doi: 10.1038/srep34949.

Quantitative Profiling of Single Formalin Fixed Tumour Sections: proteomics for translational research.

Author information

1
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
2
Department of Human Genetics, Research Institute of the McGill University Health Network, McGill University, Montreal, Canada.
3
Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
4
Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
5
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Although re-sequencing of gene panels and mRNA expression profiling are now firmly established in clinical laboratories, in-depth proteome analysis has remained a niche technology, better suited for studying model systems rather than challenging materials such as clinical trial samples. To address this limitation, we have developed a novel and optimized platform called SP3-Clinical Tissue Proteomics (SP3-CTP) for in-depth proteome profiling of practical quantities of tumour tissues, including formalin fixed and paraffin embedded (FFPE). Using single 10 μm scrolls of clinical tumour blocks, we performed in-depth quantitative analyses of individual sections from ovarian tumours covering the high-grade serous, clear cell, and endometrioid histotypes. This examination enabled the generation of a novel high-resolution proteome map of ovarian cancer histotypes from clinical tissues. Comparison of the obtained proteome data with large-scale genome and transcriptome analyses validated the observed proteome biology for previously validated hallmarks of this disease, and also identified novel protein features. A tissue microarray analysis validated cystathionine gamma-lyase (CTH) as a novel clear cell carcinoma feature with potential clinical relevance. In addition to providing a milestone in the understanding of ovarian cancer biology, these results show that in-depth proteomic analysis of clinically annotated FFPE materials can be effectively used as a biomarker discovery tool and perhaps ultimately as a diagnostic approach.

PMID:
27713570
PMCID:
PMC5054533
DOI:
10.1038/srep34949
[Indexed for MEDLINE]
Free PMC Article

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