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

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Hughes CS,McConechy MK,Cochrane DR,Nazeran T,Karnezis AN,Huntsman DG,Morin GB

doi

10.1038/srep34949

subject

Has Abstract

pub_date

2016-10-07 00:00:00

pages

34949

issn

2045-2322

pii

srep34949

journal_volume

6

pub_type

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