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

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.

Potential tumor biomarkers identified in ovarian cyst fluid by quantitative proteomic analysis, iTRAQ

“…This difference between benign and malignant tumors is supported by another study performed by our group, where we analysed benign and malignant samples using SELDI-TOF MS [2]. We had therefore several reasons why SAA4 is an interesting choice for further evaluation as a potential biomarker in ovarian cancer.…”

“…Our previous data showed that proteins, which are abundant in the blood, are even more abundant in cyst fluid [18,2]. Thus, beforehand removal of these proteins from the cyst fluid is required for the MS analysis to be able to detect potential tumor-specific biomarkers.…”

“…The five-year relative survival ranges from 90% for patients diagnosed with stage I tumors to only 35% for patients with advanced staged tumors, III or IV, according to the International Federation of Gynaecology and Obstetrics (FIGO) [2,3]. Thus, early detection seems to be the single most important factor for improving survival rates for patients with EOC.…”

Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point‐of‐care test for epithelial ovarian cancer: an observational study

“…Several studies exploring OCF for biomarker analysis found it to have little use for discriminating between benign and malignant tumours . One study suggested that OCF contained tumour‐specific biomarkers, but this study had several limitations.…”

Performance of ovarian cyst fluid fine‐needle aspiration cytology

“…Studies have found that ovarian cyst fluid contains many protein biomarkers that may be used for cancer detection. Benign and malignant cysts contain statistically different levels of protein C inhibitor, apolipoprotein C‐I and C‐III, serum amyloid 4, and transthyretin . Recently, the evaluation of DNA from ovarian cyst fluid using a multiplex polymerase chain reaction‐based assay identified tumor‐specific genetic mutations not found in benign tumors or nonneoplastic cases .…”