Abstract
The platelet-activating factor receptor (PAFR) and its ligand (PAF) are important inflammatory mediators that are overexpressed in ovarian cancer. The receptor is an important player in ovarian cancer development. In this study, we aimed to evaluate the prognostic value of PAFR in epithelial ovarian cancer (EOC) and the potential use of its antagonist, rupatadine, as an experimental treatment. Tissue microarrays of ovarian cancer patients, most markedly those with a non-mucinous subtype, immunohistochemically overexpressed PAFR. Elevated cytoplasmic PAFR expression was found to significantly and independently impair patients’ overall and recurrence-free survival (OS: median 83.48 vs. 155.03 months; p = 0.022; RFS: median 164.46 vs. 78.03 months; p = 0.015). In vitro, the serous ovarian cancer subtypes especially displayed an elevated PAFR gene and protein expression. siRNA knockdown of PAFR decreased cell proliferation significantly, thus confirming the receptor’s protumorigenic effect on ovarian cancer cells. The clinically approved PAFR antagonist rupatadine effectively inhibited in vitro cell proliferation and migration of ovarian cancer cells. PAFR is a prognostic marker in ovarian cancer patients and its inhibition through rupatadine may have important therapeutic implications in the therapy of ovarian cancer patients.
Highlights
Ovarian cancer is one of the five leading types of cancer death among women of all ages [1]
The results of this study demonstrate the clinical importance of platelet-activating factor receptor (PAFR) expression in ovarian cancer patients
It has been shown that PAFR is overexpressed in ovarian cancer samples [11]
Summary
Ovarian cancer is one of the five leading types of cancer death among women of all ages [1]. The outcome of ovarian cancer patients has remained poor, with a five-year survival rate of less than 45% [2]. The high case fatality rate of ovarian cancer is mostly attributed to late-stage diagnosis due to an occult growth of the tumor within the peritoneal cavity and a lack of screening methods. Debulking surgery is the most effective curative treatment choice. Adjuvant platinum-based chemotherapy combined with anti-angiogenic agents or followed by poly-ADP-ribose-polymerase inhibitors are established treatment options [3]. Most ovarian cancer patients are diagnosed when metastasis has already occurred [4]. It is vital to develop new and effective prognostic and therapeutic options
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