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Open Access Research

Ovarian cyst fluid is a rich proteome resource for detection of new tumor biomarkers

Björg Kristjansdottir1*, Karolina Partheen1, Eric T Fung2, Janusz Marcickiewicz1, Christine Yip2, Mats Brännström1 and Karin Sundfeldt1

Author Affiliations

1 Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, University of Gothenburg, S-413 45, Gothenburg, Sweden

2 Vermillion, Inc., Fremont, CA, USA

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Clinical Proteomics 2012, 9:14  doi:10.1186/1559-0275-9-14

Published: 27 December 2012

Abstract

Background

We aimed to investigate the use of ovarian cyst fluid as a source for biomarker discovery and to find novel biomarkers for use in the diagnosis of epithelial ovarian tumors.

Results

Ovarian cyst fluids from 218 women were collected and 192 (benign n = 129, malignant n = 63) were analyzed using mass spectrometry. 1180 peaks were detected, 221 of which were differently expressed between benign and malignant ovarian tumors. Seventeen peaks had receiver operating curve and area under the curve values >0.70; the majority of these represented peaks for apolipoproteins C-III and C-I (ApoC-I), transthyretin (TTR), serum amyloid A4 (SAA4), and protein C inhibitor (PCI). ApoC-III, PCI, and serum CA125, with an ROC AUC 0.94 was the best combination for diagnosing epithelial ovarian cancer. ApoC-III and PCI was analyzed with ELISA in the original cohort (n = 40) and in 40 new cyst fluid samples for confirmation with an independent method and validation. Results from MS and ELISA for ApoC-III correlated well (p = 0.04). In the validation set, ApoC-III was significantly (p = 0.001) increased in the malignant epithelial ovarian cancers.

Conclusions

Fluid from ovarian cysts connected directly to the primary tumor harbor many possible new tumor-specific biomarkers. Biomarkers found in ovarian cyst fluid may be used as molecular imaging targets for early diagnostics and prediction of therapy. Plasma abundant proteins are also influencing the cystic fluid proteome. Methods for isolating less frequent cyst fluid proteins are needed.

Keywords:
Biomarkers; Cyst fluid; Epithelial ovarian cancer; Ovarian cyst; Proteomic