Ascitic autotaxin as a potential prognostic, diagnostic, and therapeutic target for epithelial ovarian cancer.

ABSTRACT

BACKGROUND: Malignant ascites contributes to the metastatic process by facilitating the multifocal dissemination of ovarian tumour cells onto the peritoneal surface. However, the prognostic and diagnostic relevance of ascitic fluid remains largely unknown. Herein, we investigated the potential clinical value and therapeutic utility of ascitic autotaxin (ATX) in epithelial ovarian cancer (EOC). METHODS: ATX expression was assessed in clinical samples. Spheroid-forming assay, real-time PCR, western blot analysis, invadopodia assay, and adhesion assays were performed. RESULTS: Ascitic ATX expression was highly elevated in patients with ovarian cancer compared to those with benign ascites and was associated with advanced stage, high grade, and a short disease-free period in patients with EOC. Combining the diagnostic ability of ascitic ATX and serum CA-125 levels significantly improved the area under the curve (AUC) value for EOC compared to serum CA125 level alone. This marker combination showed a large odds ratio for short disease-free period in high-risk EOC groups. Functional studies revealed that ascitic ATX was required for maintaining cancer stem cell-like characteristics and invadopodia formation. CONCLUSION: Ascitic ATX levels may serve as a useful prognostic indicator for predicting aggressive behaviour in EOC. ATX-linked invadopodia are a potential target to prevent peritoneal dissemination in ovarian cancer.