Document Detail


In-Depth Proteomics of Ovarian Cancer Ascites: Combining Shotgun Proteomics and Selected Reaction Monitoring Mass Spectrometry.
MedLine Citation:
PMID:  21491939     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Epithelial ovarian cancer (EOC) is the most common gynecological cancer and the ninth most common cancer overall. Major problems associated with EOC include poorly characterized disease progression, disease heterogeneity, lack of early detection markers and the development of chemoresistance. Early detection and treatment of EOC would significantly benefit from routine screening tests on available biofluids. We built on our experience in analyzing ovarian cancer ascites and present an analysis pipeline that combines discovery-based proteomics, bioinformatics prioritization and targeted proteomics quantification using Selected Reaction Monitoring Mass Spectrometry (SRM-MS). Ascitic fluids from patients with serous-type epithelial ovarian cancer were analyzed using comprehensive shotgun proteomics and compared to noncancerous ascitic fluids from patients with benign ovarian tumors. Integration of our data with published mRNA transcriptomic and proteomic data sets led to a panel of 51 candidate proteins. Systematic SRM-MS assay development was performed for a subset of these proteins using both synthetic peptides (13 proteins) and stable isotope labeled standards (4 proteins). Subsequently, precise relative quantification by stable isotope dilution-SRM (SID-SRM) in independent ascites and serum samples was performed as a proof-of-concept validation. The analysis strategy outlined here lays the foundation for future experiments using both larger numbers of patient samples and additional candidate proteins, and provides a template for the proteomics-based discovery of cancer biomarkers.
Authors:
Sarah Elschenbroich; Vladimir Ignatchenko; Blaise Clarke; Steve E Kalloger; Paul C Boutros; Anthony O Gramolini; Patricia Shaw; Igor Jurisica; Thomas Kislinger
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-14
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Ontario Cancer Institute, University Health Network , Toronto, Canada.
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