title: Diagnostic Value of Serum Angiogenesis Markers in Ovarian Cancer Using Multiplex Immunoassay.
abstract: As cancer development involves pathological vessel formation, 16 angiogenesis markers were evaluated as potential ovarian cancer (OC) biomarkers. Blood samples collected from 172 patients were divided based on histopathological result: OC (n= 38), borderline ovarian tumours (n= 6), non-malignant ovarian tumours (n= 62), healthy controls (n= 50) and 16 patients were excluded. Sixteen angiogenesis markers were measured using BioPlex Pro Human Cancer Biomarker Panel 1 immunoassay. Additionally, concentrations of cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) were measured in patients with adnexal masses using electrochemiluminescence immunoassay. In the comparison between OC vs. non-OC, osteopontin achieved the highest area under the curve (AUC) of 0.79 (sensitivity 69%, specificity 78%). Multimarker models based on four to six markers (basic fibroblast growth factor-FGF-basic, follistatin, hepatocyte growth factor-HGF, osteopontin, platelet-derived growth factor AB/BB-PDGF-AB/BB, leptin) demonstrated higher discriminatory ability (AUC 0.80-0.81) than a single marker (AUC 0.79). When comparing OC with benign ovarian tumours, six markers had statistically different expression (osteopontin, leptin, follistatin, PDGF-AB/BB, HGF, FGF-basic). Osteopontin was the best single angiogenesis marker (AUC 0.825, sensitivity 72%, specificity 82%). A three-marker panel consisting of osteopontin, CA125 and HE4 better discriminated the groups (AUC 0.958) than HE4 or CA125 alone (AUC 0.941 and 0.932, respectively). Osteopontin should be further investigated as a potential biomarker in OC screening and differential diagnosis of ovarian tumours. Adding osteopontin to a panel of already used biomarkers (CA125 and HE4) significantly improves differential diagnosis between malignant and benign ovarian tumours.
authors.affiliation: Gynecologic Oncology Department, Poznan University of Medical Sciences, Polna 33, 60-535 Poznań, Poland. agnieszka0lemanska@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Horala
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. agataswiatly@gmail.com.
authors.forename: Agata
authors.initials: A
authors.lastname: Swiatly
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. jmatysiak@ump.edu.pl.
authors.forename: Jan
authors.initials: J
authors.lastname: Matysiak
authors.affiliation: Gynecologic Oncology Department, Poznan University of Medical Sciences, Polna 33, 60-535 Poznań, Poland. paulina@gmx.ch.
authors.forename: Paulina
authors.initials: P
authors.lastname: Banach
authors.affiliation: Gynecologic Oncology Department, Poznan University of Medical Sciences, Polna 33, 60-535 Poznań, Poland. ewamarkwitz@poczta.fm.
authors.forename: Ewa
authors.initials: E
authors.lastname: Nowak-Markwitz
authors.affiliation: Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland. zkokot@ump.edu.pl.
authors.forename: Zenon J
authors.initials: ZJ
authors.lastname: Kokot
mesh_terms: D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000097:blood; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008875:Middle Aged; D060787:Neoplasm Grading; D009389:Neovascularization, Pathologic / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D012372:ROC Curve
chemical_list: D043925:Angiogenesis Inducing Agents; D014408:Biomarkers, Tumor
keywords: angiogenesis; biomarkers; ovarian cancer