Abstract B27: Cellular retinoic acid binding protein 2 (CRABP2) is a novel biomarker and potential therapeutic target for high-grade serous ovarian carcinomas

Abstract

Abstract Ovarian cancer ranks fifth in cancer deaths among women in the United States, accounting for more deaths than any other gynecologic cancer. There is an unmet medical need for biomarkers that can detect high-grade serous ovarian carcinoma (HGSOC) at an early stage. Our laboratory evaluated the biomarker potential of cellular retinoic acid binding protein 2 (CRABP2). Using Western blots (WB) and immunohistochemistry (IHC), we show that CRABP2 is expressed and secreted by HGSOC cells and tissues and is absent in normal fallopian tube (FT) epithelium. CRABP2 expression was associated with poor overall survival in patients with HGSOC. Proteomic analyses quantified specific secretion of CRABP2 in conditioned media from HGSOC cell lines, primary ascites-derived tumor cells, and serum from HGSOC patients. Expression of CRABP2 was positively associated with CRABP2 copy number amplifications by mining The Cancer Genome Atlas database. In addition, DNA methylation studies identified a putative enhancer downstream of CRABP2 that is hyper-methylated in fallopian tube epithelia (FTE) tissue and hypomethylated in HGSOC cells and tissues that expressed CRABP2. Inhibition of DNA methylation with DNA methytransferase (DNMT) inhibitors resulted in robust expression of CRABP2 protein in FT cell lines. Finally, a finding supported by CRABP2 knockdown experiments showed that CRABP2 loss triggers cell death in HGSOC cell lines. In conclusion, CRABP2 may serve as a novel biomarker for HGSOC with clinical potential as a therapeutic target. Citation Format: Yi Feng, Michael Gillette, Eric Kuhn, David Klinkebiel, Marilyn A. Mitchell, Kai Doberstein, Daniele Chaves-Moreira, Sho Sato, Haineng Xu, Brett Bomwell, Michelle S. Hirsch, Carolina Reyes, Adam R. Karpf, Michael J. Birrer, Steven J. Skates, Steven A. Carr, Ronny Drapkin. Cellular retinoic acid binding protein 2 (CRABP2) is a novel biomarker and potential therapeutic target for high-grade serous ovarian carcinomas [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B27.