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    Identification of novel candidate biomarkers of epithelial ovarian cancer by profiling the Secretomes of three-dimensional genetic models of ovarian carcinogenesis.

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    Authors
    Lawrenson, Kate
    Mhawech-Fauceglia, Paulette
    Worthington, Jenny
    Spindler, Tassja J.
    O'Brien, Darragh
    Lee, Janet M.
    Spain, Georgia
    Sharifian, Maryam
    Wang, Guisong
    Darcy, Kathleen M.
    Pejovic, Tanja
    Sowter, Heidi M. cc
    Timms, John F.
    Gayther, Simon A.
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    Affiliation
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
    University of Derby
    Issue Date
    2014-09-09
    
    Metadata
    Show full item record
    Abstract
    Epithelial ovarian cancer is still considered the most lethal gynecological malignancy and improved early detection of ovarian cancer is crucial to improving patient prognoses. To address this need, we tested whether candidate EOC biomarkers can be identified using three-dimensional in vitro models. We quantified changes in the abundance of secreted proteins in a 3D genetic model of early-stage EOC, generated by expressing CMYC and KRAS(G12V) in TERT-immortalized normal ovarian epithelial cells. Cellular proteins were labeled in live cells using stable isotopic amino acid analogues, and secreted proteins identified and quantified using liquid chromatography-tandem mass spectrometry. 37 and 55 proteins were differentially expressed by CMYC and CMYC+KRAS(G12V) expressing cells respectively (P<0.05; >2-fold). We evaluated expression of the top candidate biomarkers in ˜210 primary EOCs: CHI3L1 and FKBP4 are both expressed by >96% of primary EOCs, and FASN and API5 are expressed by 86% and 75% of cases. High expression of CHI3L1 and FKBP4 was associated with worse patient survival (P=0.042 and P=0.002 respectively). Expression of LGALS3BP was positively associated with recurrence (P=0.0001) and suboptimal debulking (P=0.018) suggesting that these proteins may be novel prognostic biomarkers. Furthermore, within early stage tumours (I/II), high expression of API5, CHI3L1 and FASN was associated with high tumour grade (P=3x10(-4) , P=0.016, P=0.010, respectively). We show in vitro cell biology models of early-stage cancer development can be used to identify novel candidate biomarkers for disease, and report the identification of proteins that represent novel potential candidate diagnostic and prognostic biomarkers for this highly lethal disease. © 2014 Wiley Periodicals, Inc.
    Citation
    Lawrenson, K. et al (2015) 'Identification of novel candidate biomarkers of epithelial ovarian cancer by profiling the Secretomes of three-dimensional genetic models of ovarian carcinogenesis.' International Journal of Cancer, 137 (8), pp. 1806-1817.
    Publisher
    Wiley
    Journal
    International Journal of Cancer
    URI
    http://hdl.handle.net/10545/344422
    DOI
    10.1002/ijc.29197
    PubMed ID
    25204737
    Type
    Article
    Language
    en
    ISSN
    1097-0215
    ae974a485f413a2113503eed53cd6c53
    10.1002/ijc.29197
    Scopus Count
    Collections
    Human Sciences Research Centre

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