Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer.

Zhaoxia Liu,Tingtao Chen,Hui Hu,Rongna Yun,Xiaolin Yu,Genhua Huang,Buzhen Tan

doi:10.1155/2016/5953498

Abstract

Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p < 0.01). In tumor tissues, Notch3 expression and pS6 expression were negatively associated with age (p > 0.05) but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p < 0.05 or p < 0.01). A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p < 0.01), in which the clinical stage (p < 0.05) and Notch3 expression (p < 0.01) played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.

Highlights

Ovarian cancer represents one of the most aggressive neoplastic diseases in women, and 75% patients are diagnosed at advanced stage due to the lack of biomarkers for early diagnosis [1]
We found that Notch3 expression and pS6 expression were negatively associated with age (p > 0.05) but were positively associated with clinical stage, pathological grading, histological type, lymph node metastasis, and ascites
The Notch signaling cascade is critical for cell proliferation, differentiation, development, and homeostasis [13], and deregulated Notch signaling is found in various diseases (e.g., T-cell leukemia, breast cancer, prostate cancer, colorectal cancer and lung cancer, and central nervous system malignancies) [14]

Summary

Introduction

Ovarian cancer represents one of the most aggressive neoplastic diseases in women, and 75% patients are diagnosed at advanced stage due to the lack of biomarkers for early diagnosis [1]. In 2012, ovarian cancer occurred in 239,000 women and caused 152,000 deaths worldwide and was more common in North America and Europe than in Africa and Asia [2]. A type of Notch receptor (Notch, Notch, Notch, and Notch4), plays an important role in promoting ovarian tumorigenesis, cancer progression, and chemotherapy resistance via activating the PI3K/Akt/mTOR signaling pathway [4]. Ribosomal S6 kinase (S6K), a downstream effector of the PI3K/Akt pathway, is frequently activated in human ovarian cancer [5] and is significantly more prevalent in malignant tumors than in benign lesions. PS6 kinase is involved in other aspects of cancer progression in addition to its well-established role in regulating proliferation and cell survival [5,6,7] Ribosomal S6 kinase (S6K), a downstream effector of the PI3K/Akt pathway, is frequently activated in human ovarian cancer [5] and is significantly more prevalent in malignant tumors than in benign lesions. pS6 kinase is involved in other aspects of cancer progression in addition to its well-established role in regulating proliferation and cell survival [5,6,7]

Methods

Results

Conclusion