14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer.

Abstract

PURPOSE:

14-3-3ζregulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζis associated with ovarian cancer prognosis.

MATERIALS AND METHODS:

We examined 14-3-3ζexpression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζexpression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment.

RESULTS:

Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζexpression, and 14-3-3ζoverexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζoverexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζexpression group, but not reached in the low 14-3-3ζexpression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζby RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death.

CONCLUSION:

14-3-3ζoverexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζcould be a therapeutic option that enhances the antitumor activity of cisplatin.

• Authors: Hyun Jung Kim, Sun Hee Sung, Chan Young Kim, Moon Kyoung Bae, Min Sun Cho, Yun Hwan Kim, Seung Cheol Kim, Woong Ju
• Journal: Yonsei medical journal (Yonsei Med J) Vol. 59 Issue 1 Pg. 51-56 (Jan 2018) ISSN: 1976-2437 [Electronic] Korea (South)
• PMID: 29214776 (Publication Type: Journal Article)
• Copyright: © Copyright: Yonsei University College of Medicine 2018

Chemical References

• 14-3-3 Proteins
• YWHAZ protein, human
• Cisplatin

Topics

• 14-3-3 Proteins (metabolism)
• Adult
• Aged
• Cell Line, Tumor
• Cisplatin (therapeutic use)
• Disease-Free Survival
• Down-Regulation
• Female
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• Immunohistochemistry
• Middle Aged
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Prognosis
• Young Adult