Quantitative profiling of single formalin fixed tumour sections: Proteomics for translational research

Christopher S. Hughes, Melissa K. Mcconechy, Dawn R. Cochrane, Tayyebeh Nazeran, Anthony Karnezis, David G. Huntsman, Gregg B. Morin

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Article number34949
JournalScientific Reports
Volume6
DOIs
StatePublished - Oct 7 2016
Externally publishedYes

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Translational Medical Research
Proteome
Proteomics
Formaldehyde
Neoplasms
Paraffin
Ovarian Neoplasms
Cystathionine gamma-Lyase
Tissue Array Analysis
Gene Expression Profiling
Biomarkers
Clinical Trials
Genome
Technology
Carcinoma
Messenger RNA
Genes
Proteins

ASJC Scopus subject areas

  • General

Cite this

Hughes, C. S., Mcconechy, M. K., Cochrane, D. R., Nazeran, T., Karnezis, A., Huntsman, D. G., & Morin, G. B. (2016). Quantitative profiling of single formalin fixed tumour sections: Proteomics for translational research. Scientific Reports, 6, [34949]. https://doi.org/10.1038/srep34949

Quantitative profiling of single formalin fixed tumour sections : Proteomics for translational research. / Hughes, Christopher S.; Mcconechy, Melissa K.; Cochrane, Dawn R.; Nazeran, Tayyebeh; Karnezis, Anthony; Huntsman, David G.; Morin, Gregg B.

In: Scientific Reports, Vol. 6, 34949, 07.10.2016.

Research output: Contribution to journalArticle

Hughes, Christopher S. ; Mcconechy, Melissa K. ; Cochrane, Dawn R. ; Nazeran, Tayyebeh ; Karnezis, Anthony ; Huntsman, David G. ; Morin, Gregg B. / Quantitative profiling of single formalin fixed tumour sections : Proteomics for translational research. In: Scientific Reports. 2016 ; Vol. 6.
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