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

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.

The Role of Notch3 in Cancer

“…Notch3 expression is significantly higher in ovarian cancer compared with normal ovaries or benign ovarian tumors . More than twofold higher expression of Notch3 was detected in 63% of serous ovarian carcinomas compared with benign ovarian tissue .…”

“…Notch3 expression was associated with higher tumor grade, lymph node (LN) and distant metastasis, and higher clinical stage in ovarian cancer . It is known that Notch3 promotes resistance to anoikis, a process involved in programed cell death after detachment from anchoring extracellular matrix .…”

“…High Notch3 expression is associated with tumor recurrence and poor survival . High Notch3 expression was associated with shorter overall survival and worse progression‐free survival in recurrent high‐grade serous carcinoma (HGSC) of the ovary.…”

“…Changes in Notch activity have been associated with several benign and malignant diseases . Although the primary function of Notch seems to be regulation of vasculogenesis, in which its dysregulation has been linked to a number of vasculopathies, it can also have tumor suppressive or oncogenic roles (Table ).…”

Inhibition effect of triptolide on human epithelial ovarian cancer via adjusting cellular immunity and angiogenesis

“…Numerous studies indicate that the mechanism of tumor occurrence, development, invasion, metastasis and resistance is complex (4)(5)(6)(7)(8)(9). As one of the most well-known natural products, triptolide (TPL) had been used as an anti-inflammatory agent for rheumatoid arthritis for a long time in China, and was also recognized as a potential medicine for various types of cancers (10)(11)(12)(13)(14)(15)(16) although some researchers showed its potential toxicity on animal liver, kidney, testes, ovary and heart (17).…”