EP569 Potential role of PAI-1 in endometrial cancer progression and its regulation by epigenetic mechanisms

Introduction/Background Endometrial cancer (EC) is the most prevalent gyneacological cancer. It presents two subtypes, (Type-1 and Type-2), being the lately associated to worse prognosis and increased epithelial-to-mesenchymal transition (EMT). A growing evidence supports that uPA and PAI-1 play a role in solid tumour progression, though the exact role of PAI-1 and its epigenetic regulation in EC has not been completely established yet. Methodology 67 patients with EC and 36 control women were included. 5 miRNAs targeting PAI-1 mRNA (namely miR-99a-5p, miR-143-3p, miR-145-5p, miR-196b-5p y miR-301a-3p) were selected from miRNA expression profiles (Affymetrix, GeneChipmiRNA 2.0) and validated by RT-qPCR. mRNA levels of E-cadherin, Vimentin, Fibronectin, Snail1 and Twist were assessed by RT-qPCR; PAI-1 tissue and plasma levels by ELISA (DuoSet). Results At the tissue level, PAI-1 is over-expressed in EC in comparison to control endometria (CE) (88.67±12.65 vs. 65.89±9.39 pg/mg), and is significantly increased in Type-2 vs. Type-1 EC (124.43±18.31 vs. 65.90±13.57 pg/mg; p=0.02). At the plasma level, PAI-1 increases in EC vs. control plasma (3.06±0.34 vs. 0.99±0.19 ng/mL, p Conclusion PAI-1 plasma and tissue levels are over-expressed in EC vs. CE, but only in tissues it is over-expressed in the worst-prognose subtype, which is associated with increased EMT markers. This local action of PAI-1 might be mediated by down-regulation of miR-196b-5p. Disclosure All authors have declared no conflicts of interest. This work has been supported by grants from ISCIII (PI17/01945). J. M-A. is supported by a FETH 2016-2018 award and a post-doctoral grant (APOSTD/2019/087).