title: Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.
abstract: Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here the most comprehensive survey of the chicken blood proteome to date.
authors.affiliation: 1 System Biology Division, Zhejiang-California International Nanosystem Institute (ZCNI), Zhejiang University , Hangzhou, China .
authors.forename: Yingying
authors.initials: Y
authors.lastname: Ma
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Sun
authors.forename: Ricardo
authors.initials: R
authors.lastname: de Matos
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D002645:Chickens / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000662:veterinary*; D010051:Ovarian Neoplasms / Q000097:blood / Q000662:veterinary*; D019151:Peptide Library; D011201:Poultry Diseases / Q000097:blood*; D040901:Proteomics; D057170:Translational Research, Biomedical
chemical_list: D030161:Avian Proteins; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D019151:Peptide Library