EP220/#471 High expression of phosphodiesterase 1 (PDE1A) promotes poor prognosis and associated with platinum based chemotherapy resistance in epithelial ovarian cancer

Objectives

Phosphodiesterase 1A (PDE1A) belongs to phosphohydrolytic enzymes resulting integration of Ca2+ and cyclic nucleotide mediate signaling in various cancers. However, its role in epithelial ovarian cancer (EOC) has not been clarified yet. Therefore, in this study we aim to evaluate the functional role and clinicopathological significance of PDE1A in EOC

Methods

Expression level of PDE1A was screened by RNA sequencing of EOCs and normal ovarian epithelial tissues, GEO dataset and immunohistochemitry of EOCs. Associations of clinicopathological features and prognosis with PDE1A in EOC patients were analyzed and the its functional roles were evaluated in EOC cell lines.

Results

Significantly overexpression of PDE1A was observed in EOCs compared to borderline, benign and normal nonadjacent ovarian epithelial tissues by IHC. Also, overexpression of PDE1A was significantly associated with serous, high grade, and advanced FIGO stage. Importantly, overexpression of PDE1A was associated poor overall survival and disease free survival compared with low expression of PDE1A in EOCs, and was associated with platinum based chemotherapy resistance. In vitro results demonstrated the knockdown of PDE1A was significantly associated with decreased cell invasion, migration, proliferation, and colony forming abilities supporting the oncogenic role in EOC. Also, FACS annexin V double staining assay revealed significant increased apoptosis in PDE1A knockdown EOC cell lines.

Conclusions

Our study is the first work to identify an oncogenic role and association with chemotherapy resistance of PDE1A in EOC which may provide insights into the application of PDE1A as a novel predictive biomarker for prognosis and chemotherapy and a potential therapeutic target in EOC patients