Abstract 4718: Filamin A interacting protein 1-like is a marker of prognosis, progression and chemosensitivity in ovarian cancer

Abstract

Abstract Purpose: The WNT/β-catenin pathway and the resulting epithelial-to-mesenchymal transition (EMT) play a key role in ovarian cancer progression and chemoresistance. Filamin A interacting protein 1-like (FILIP1L) enhances β-catenin degradation, thereby inhibiting canonical WNT signaling and EMT. FILIP1L is a tumor suppressor whose expression is down-regulated by promoter hyper-methylation in ovarian cancer. FILIP1L down-regulation is inversely correlated with the invasive potential of ovarian cancer cells. However, the clinical relevance of FILIP1L down-regulation in ovarian cancer progression has yet to be addressed. Experimental design: To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway and chemoresistance, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic. Their expression was evaluated with clinicopathological characteristics including FIGO stage and chemosensitivity, and correlated with overall and disease-free survival by Kaplan-Meier plots and Cox proportional hazards model. Results: We demonstrated that FILIP1L expression decreased with tumor progression, resulting in a significant difference between primary and metastatic ovarian cancer samples. In contrast, levels of β-catenin and SLUG increased with tumor progression. Furthermore, tumors that were resistant to platinum/paclitaxel combination therapy showed a significant reduction in FILIP1L expression when compared to sensitive tumors, contrary to SLUG expression, which was significantly higher. The expression of FILIP1L was negatively correlated with the expression of β-catenin and SLUG, whereas β-catenin expression was positively correlated with SLUG expression, suggesting a link between FILIP1L and the WNT/β-catenin pathway in ovarian cancer. Moreover, patients with low FILIP1L expression showed a median overall survival and disease-free survival of 60 and 19 months, respectively, whereas patients with high FILIP1L expression had not yet reached median overall and disease-free survival at their 120 month follow-up. Notably, low FILIP1L expression was independent negative prognostic factor with respect to overall and disease-free survival. Conclusions: Our study provides the first clinical relevance of FILIP1L in human cancer, and suggests that FILIP1L may be a novel biomarker for good prognosis and lower probability of recurrence in ovarian cancer patients. Citation Format: Mijung Kwon, Jae-Hoon Kim, Chel Hun Choi, Joon-Yong Chung, Stephen Hewitt, Steven Libutti. Filamin A interacting protein 1-like is a marker of prognosis, progression and chemosensitivity in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4718. doi:10.1158/1538-7445.AM2017-4718