High levels of KAP1 expression are associated with aggressive clinical features in ovarian cancer.

Yanfen Cui,Xin Fu,Shilei Xu,Jingwen Feng,Guoguang Ying,Shaobin Yang

doi:10.3390/ijms16010363

Abstract

KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230–0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer.

Highlights

Epithelial ovarian cancer is the deadliest gynecological malignancy and the second leading cause of cancer-related deaths among women worldwide [1]
To investigate the expression of KAP1 in ovarian cancer tissues and normal ovarian tissues, immunohistochemistry (IHC) was applied to show that KAP1 was expressed in both tumor cells and mesenchymal cells, and localized to the cell nucleus (Figure 1)
The results showed that the expression level of KAP1 was higher in ovarian cancer samples than non-tumor ovarian tissues (Figure 1A–D), and the positive rates of

Summary

Introduction

Epithelial ovarian cancer is the deadliest gynecological malignancy and the second leading cause of cancer-related deaths among women worldwide [1]. About 22,240 women were diagnosed with invasive epithelial ovarian cancer in the United States in 2013 [2]. Ovarian cancer is relatively uncommon in China, but an increase in the incidence has been reported. Since ovarian cancer has no early typical symptoms and effective diagnostic methods, and is located deep within the pelvis and difficult to assess, more than 70% of patients are diagnosed at an advanced stage [4]. The prognosis of ovarian cancer patients is very poor. It is urgent to find new biomarkers, which are able to identify specific patients who may benefit from aggressive therapies and predict the prognosis of epithelial ovarian cancer [5,6]

Methods

Results

Conclusion