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

Timms, John F.
Gayther, Simon A.
Affiliation
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USAUniversity of Derby
Issue Date
2014-09-09
Metadata
Show full item recordAbstract
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
WileyJournal
International Journal of CancerDOI
10.1002/ijc.29197PubMed ID
25204737Type
ArticleLanguage
enISSN
1097-0215ae974a485f413a2113503eed53cd6c53
10.1002/ijc.29197
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