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Int. J. Mol. Sci. 2017, 18(1), 123; doi:10.3390/ijms18010123

Diagnostic Value of Serum Angiogenesis Markers in Ovarian Cancer Using Multiplex Immunoassay

1
Gynecologic Oncology Department, Poznan University of Medical Sciences, Polna 33, 60-535 Poznań, Poland
2
Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland
These authors contributed equally to the work.
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 17 November 2016 / Revised: 14 December 2016 / Accepted: 20 December 2016 / Published: 10 January 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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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. View Full-Text
Keywords: ovarian cancer; biomarkers; angiogenesis ovarian cancer; biomarkers; angiogenesis
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Horala, A.; Swiatly, A.; Matysiak, J.; Banach, P.; Nowak-Markwitz, E.; Kokot, Z.J. Diagnostic Value of Serum Angiogenesis Markers in Ovarian Cancer Using Multiplex Immunoassay. Int. J. Mol. Sci. 2017, 18, 123.

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