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. 2013 Nov 15;6(1):79.
doi: 10.1186/1757-2215-6-79.

Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer

Ioannis Hatzipetros  1 , Peter Gocze, Tamas Koszegi, Akos Jaray, Laszlo Szereday, Beata Polgar, Nelli Farkas, Balint Farkas
Affiliations

Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer

Ioannis Hatzipetros et al. J Ovarian Res. .

Abstract

Objective: Recently, 14-3-3 zeta protein was identified as a potential serum biomarker of epithelial ovarian cancer (EOC). The goal of this study was to investigate the clinical potential of 14-3-3 zeta protein for monitoring EOC progression compared with CA-125 and HE4.

Design: Prospective follow-up study.

Setting: University of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary).

Population: Thirteen EOC patients with advanced stage (FIGO IIb-IIIc) epithelial ovarian cancer that underwent radical surgery and received six consecutive cycles of first line chemotherapy (paclitaxel, carboplatin) in 21-day intervals.

Methods: Pre- and post-chemotherapy computed tomography (CT) scans were performed. Serum levels of CA-125, HE4, and 14-3-3 zeta protein were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative electrochemiluminescence assay (ECLIA).

Main outcome measures: Serum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans.

Results: Serum levels of CA-125 and HE4 were found to significantly decrease following chemotherapy, and this was consistent with the decrease in lesion size detected post-chemotherapy. In contrast, 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus EOC patients.

Conclusions: Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC.

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Figures

Figure 1
Figure 1
Axial CT slices of patient # 3 after contrast material was intravenously administered. A _target lesion with a SLD of 84 mm is localized near the minor pelvis before (A) and after (C) six cycles of first-line chemotherapy. (B) The arrow represents a mesenteric peritoneal carcinosis (non-_target lesion) in the same patient that is level with the lower edge of the liver prior to chemotherapy. A significant amount of ascites associated with the non-_target lesion is also observed (B). (D) Both non-_target lesions are absent after the completion of chemotherapy.
Figure 2
Figure 2
Mean levels of serum biomarkers (CA-125, HE4 and 14-3-3 zeta protein) measured with ELISA and ECLIA methods, and the ROMA index values. Average values of CA-125 (U/mL) +/− SEM determined by ECLIA (A) and by ELISA (D) are shown according to the chemotherapy cycles (consistently on each x-axis from 1 to 6). Mean concentrations of HE4 (p/M), measured by ECLIA (B) and by ELISA (E) are also shown. Furthermore average values determined by ELISA (G) of 14-3-3 zeta protein (ng/ml) are depicted. Based on the above-mentioned data, we calculated the postmenopausal ROMA index values (%) for ECLIA (C) and for ELISA (F) techniques. We represent the mean levels of 14-3-3 zeta protein (ng/mL) for each of the treatment days. Wilcoxon signed-rank test analysis was performed for each diagram, and statistical significance represented with asterisk (*) was set at p < 0.05, and (**) when p < 0.01.
Figure 3
Figure 3
Changes in CA-125, HE4, and 14-3-3 zeta protein serum levels, and ROMA index values during the six cycles of paclitaxel/carboplatin-based chemotherapy that were performed. Mean concentrations of CA-125 determined by ELISA (A) and by ECLIA (D) are shown for each of the treatment days. Mean levels of HE4 determined by ELISA (B) and ECLIA (E) are also shown for each of the treatment days. Mean concentrations of 14-3-3 zeta protein were determined by ELISA (G) are represented at each chemotherapy days. Postmenopausal ROMA index values were calculated based on ELISA (C) and ECLIA (F) data. Linear regression analysis was performed for each diagram (see r value), and statistical significance was set at p < 0.05.
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