title: Protein Z: A putative novel biomarker for early detection of ovarian cancer.
abstract: Ovarian cancer (OC) has the highest mortality of all gynaecological cancers. Early diagnosis offers an approach to achieving better outcomes. We conducted a blinded-evaluation of prospectively collected preclinical serum from participants in the multimodal group of the United Kingdom Collaborative Trial of Ovarian Cancer Screening. Using isobaric tags (iTRAQ) we identified 90 proteins differentially expressed between OC cases and controls. A second targeted mass spectrometry analysis of twenty of these candidates identified Protein Z as a potential early detection biomarker for OC. This was further validated by ELISA analysis in 482 serial serum samples, from 80 individuals, 49 OC cases and 31 controls, spanning up to 7 years prior to diagnosis. Protein Z was significantly down-regulated up to 2 years pre-diagnosis (p = 0.000000411) in 8 of 19 Type I patients whilst in 5 Type II individuals, it was significantly up-regulated up to 4 years before diagnosis (p = 0.01). ROC curve analysis for CA-125 and CA-125 combined with Protein Z showed a statistically significant (p = 0.00033) increase in the AUC from 77 to 81% for Type I and a statistically significant (p= 0.00003) increase in the AUC from 76 to 82% for Type II. Protein Z is a novel independent early detection biomarker for Type I and Type II ovarian cancer; which can discriminate between both types. Protein Z also adds to CA-125 and potentially the Risk of Ovarian Cancer algorithm in the detection of both subtypes.
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Russell
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walker
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Andrew J K
authors.initials: AJ
authors.lastname: Williamson
authors.affiliation: Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.affiliation: Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Andy
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Jatinderpal
authors.initials: J
authors.lastname: Kalsi
authors.affiliation: Biostatistics Centre, MA General Hospital, Boston, MA.
authors.forename: Steven
authors.initials: S
authors.lastname: Skates
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Alfonsina
authors.initials: A
authors.lastname: D'Amato
authors.affiliation: Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dive
authors.affiliation: SciLifeLab, Department of Oncology and Pathology, Karolinska Institutet, Tomtebodavägen 23, 171 65, Solna, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Pernemalm
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Humphryes
authors.affiliation: Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Evangelia-Ourania
authors.initials: EO
authors.lastname: Fourkala
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Whetton
authors.affiliation: Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.|Gynaecological Cancer Research Centre, Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom.|University of New South Wales, Sydney, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: Stoller Biomarker Discovery Centre and Pathology Node, Institute of Cancer Sciences, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Robert L J
authors.initials: RL
authors.lastname: Graham
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis*; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; C026080:plasma protein Z
keywords: SWATH; UKCTOCS; early detection; ovarian cancer; proteomics
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