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

2.50
Hdl Handle:
http://hdl.handle.net/10545/344422
Title:
Identification of novel candidate biomarkers of epithelial ovarian cancer by profiling the Secretomes of three-dimensional genetic models of ovarian carcinogenesis.
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. ( 0000-0002-1408-1900 ) ; Timms, John F.; Gayther, Simon A.
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.
Affiliation:
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA; University of Derby
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
Issue Date:
9-Sep-2014
URI:
http://hdl.handle.net/10545/344422
DOI:
10.1002/ijc.29197
PubMed ID:
25204737
Type:
Article
Language:
en
ISSN:
1097-0215
Appears in Collections:
Biological Sciences Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorLawrenson, Kateen
dc.contributor.authorMhawech-Fauceglia, Pauletteen
dc.contributor.authorWorthington, Jennyen
dc.contributor.authorSpindler, Tassja J.en
dc.contributor.authorO'Brien, Darraghen
dc.contributor.authorLee, Janet M.en
dc.contributor.authorSpain, Georgiaen
dc.contributor.authorSharifian, Maryamen
dc.contributor.authorWang, Guisongen
dc.contributor.authorDarcy, Kathleen M.en
dc.contributor.authorPejovic, Tanjaen
dc.contributor.authorSowter, Heidi M.en
dc.contributor.authorTimms, John F.en
dc.contributor.authorGayther, Simon A.en
dc.date.accessioned2015-02-13T16:10:36Zen
dc.date.available2015-02-13T16:10:36Zen
dc.date.issued2014-09-09en
dc.identifier.citationLawrenson, 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.en
dc.identifier.issn1097-0215en
dc.identifier.pmid25204737en
dc.identifier.doi10.1002/ijc.29197en
dc.identifier.urihttp://hdl.handle.net/10545/344422en
dc.description.abstractEpithelial 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.en
dc.languageENGen
dc.language.isoenen
dc.publisherWileyen
dc.rightsArchived with thanks to International journal of cancer. Journal international du canceren
dc.subject3D modelsen
dc.subjectOvarian canceren
dc.titleIdentification of novel candidate biomarkers of epithelial ovarian cancer by profiling the Secretomes of three-dimensional genetic models of ovarian carcinogenesis.en
dc.typeArticleen
dc.contributor.departmentDepartment of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USAen
dc.contributor.departmentUniversity of Derbyen
dc.identifier.journalInternational Journal of Canceren

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