title: 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.
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hughes
authors.affiliation: Department of Human Genetics, Research Institute of the McGill University Health Network, McGill University, Montreal, Canada.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Cochrane
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Tayyebeh
authors.initials: T
authors.lastname: Nazeran
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Karnezis
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.affiliation: Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.|Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Gregg B
authors.initials: GB
authors.lastname: Morin
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005557:Formaldehyde; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009363:Neoplasm Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010449:Peptide Mapping; D000071696:Proteogenomics; D040901:Proteomics / Q000379:methods*; D016707:Tissue Fixation; D057170:Translational Research, Biomedical
chemical_list: D009363:Neoplasm Proteins; D005557:Formaldehyde