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

Abstract

ObjectiveRecently, 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.DesignProspective follow-up study.SettingUniversity of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary).PopulationThirteen 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.MethodsPre- 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 measuresSerum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans.ResultsSerum 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.ConclusionsDetermination 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.

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma

“…Studies have shown that the 14-3-3zeta protein is overexpressed in a variety of tumor types, including HCC[29,30]. …”

Quantitative proteomic analysis of mitochondria from human ovarian cancer cells and their paclitaxel‐resistant sublines

“…The role of 14‐3‐3 ζ/δ in ovarian cancer is also controversial. Hatzipetros found that serum 14‐3‐3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus epithelial ovarian cancer (EOC) patients . However, Kobayashi demonstrate that 14‐3‐3 zeta was secreted by ascitic monocytes/macrophages from EOC patients and was present in malignant ascites of EOC patients, but the functional role for 14‐3‐3 zeta as a secreted protein was unclear .…”

“…Hatzipetros found that serum 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus epithelial ovarian cancer (EOC) patients. (34) However, Kobayashi demonstrate that 14-3-3 zeta was secreted by ascitic monocytes ⁄ macrophages from EOC patients and was present in malignant ascites of EOC patients, but the functional role for 14-3-3 zeta as a secreted protein was unclear. (35) Waldemarson et al (2012) found a gradual upregulation of 14-3-3 f ⁄ d protein when going from normal to benign to borderline to malignant tumors using iTRAQ technology, making it a biomarker of early stage ovarian cancer.…”

A cancer-related protein 14-3-3ζ is a potential tumor-associated antigen in immunodiagnosis of hepatocellular carcinoma

“…Recently, the 14-3-3ζ protein was identified as a potential serum biomarker of epithelial ovarian cancer [41, 42]. However, levels of the 14-3-3ζ protein were not found to be changed significantly as a consequence of treatment [43]. In this study, we use immunologic and molecular methods to test the possibility of 14-3-3ζ as a TAA and whether anti-14-3-3ζ antibody can be used as an early diagnostic biomarker in HCC patients.…”