title: Y-box protein-1/p18 as novel serum marker for ovarian cancer diagnosis: A study by the Tumor Bank Ovarian Cancer (TOC).
abstract: The cold shock Y-box binding protein-1 (YB-1) fulfills important roles in regulating cell proliferation and differentiation. Overexpression occurs in various tumor cells. Given the existence of extracellular YB-1 we set out to determine the diagnostic, predictive and prognostic role of serum YB-1/p18 for patients with primary epithelial ovarian cancer (EOC).
  
  
  
  The protein fragment YB-1/p18 was quantified by sandwich ELISA in serum samples from 132 healthy female volunteers and 206 patients with histological diagnosis of primary EOC. The ELISA sensitivity and specificity to detect EOC were calculated using receiver operating curves. Survival data were calculated using Kaplan Maier curves.
  
  
  
  Median age at the time of diagnosis was 60years and follow-up ended with a mean of 44.8month. 188 (91%) patients were diagnosed at advanced stages (FIGO III/IV) and 188 patients (91%) suffered from high-grade serous ovarian carcinoma. YB-1/p18 levels were significantly decreased in older patients (p=0.021). Significantly lower serum levels of YB-1/p18 were detected in the EOC cohort when compared to the control group (p<0.0001, AUC=0.827; 95% CI, 0.787-0.867). Using the expression of serum YB-1/p18 in early stages I and II cases these could be differentiated from control cases (p<0.0001, AUC=0.816; 95% CI 0.704-0.929). No other significant associations between clinical prognostic factors and YB-1/p18 serum levels were detected. Immunoblotting results with serum samples suggest that masking of epitopes by the YB-1/p18 fragment in multiprotein-complexes under non reducing conditions leads to the observed reduced ELISA readings in the EOC cohort.
  
  
  
  The quantification of fragment YB-1/p18 derived from cold shock protein YB-1 in serum samples could be useful for the early diagnosis of EOC.
authors.affiliation: Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Irena
authors.initials: I
authors.lastname: Rohr
authors.affiliation: Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Braicu
authors.affiliation: Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: En-Nia
authors.affiliation: Center for Chronic Sick Children, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Heinrich
authors.affiliation: Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Richter
authors.affiliation: Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Chekerov
authors.affiliation: Experimental and Clinical Research Center, a joint cooperation between the Max-Delbruck Center for Molecular Medicine and the Charité University Departments of Nephrology and HELIOS-Kliniken Berlin Buch, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: CellTrend, Luckenwalde, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Heidecke
authors.affiliation: Department of Nephrology and Intensive Care Medicine, Charité Universitätsmedizin, Berlin, Germany; Center for Cardiovascular Research, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.affiliation: Laboratory of Molecular Tumor Pathology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schäfer
authors.affiliation: Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Xenia
authors.initials: X
authors.lastname: Gorny
authors.affiliation: Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lindquist
authors.affiliation: Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Brandt
authors.affiliation: Gynecological Tumor Center and European Competence Center for Ovarian Cancer, Charité Universitätsmedizin, Berlin, Germany. Electronic address: jalid.sehouli@charite.de.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Clinic of Nephrology and Hypertension, Diabetes and Endocrinology, Otto-von-Guericke University, Magdeburg, Germany. Electronic address: peter.mertens@med.ovgu.de.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mertens
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D012680:Sensitivity and Specificity; D051840:Y-Box-Binding Protein 1 / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human
keywords: Chemotherapy; Cold shock proteins; Epithelial ovarian cancer; Serum marker