Abstract
BackgroundWe 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.ResultsOvarian 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.ConclusionsFluid 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.
Highlights
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
Proteomic profiling Seventeen significant peaks had Receiver operating curve (ROC) AUC values >0.70 A total of 1180 peaks were resolved by SELDI-TOF MS, and of these, 221 peaks were differently expressed (p
Several peaks in the cyst fluid were identified as albumin and other proteins that are abundant in blood [17]
Summary
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. The incidence of ovarian cancer in Europe and the United States is 11/100 000, and about 200 000 women worldwide are diagnosed with the disease each year [1]. More than 70% of all ovarian cancers are detected in the late stages (FIGO III-IV), and the five-year survival rate is only 25–30% for these patients. Ovarian cancer is detected in stage I, when the disease is still confined to the ovary, the five-year survival rate is over 85% [2]. Improvement in the diagnosis of this lethal disease is very desirable. Serum biomarkers for the early detection of EOC such as CA125
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