# Clinical and Functional Characterization of PDE1A as a Wnt/β-Catenin-Linked Biomarker of Progression and Platinum Resistance in Epithelial Ovarian Cancer

## TL;DR

This study shows that high PDE1A levels in ovarian cancer are linked to worse outcomes and resistance to platinum drugs, and that PDE1A is connected to Wnt/β-catenin signaling.

## Contribution

The study identifies PDE1A as a novel Wnt/β-catenin-linked biomarker for ovarian cancer progression and platinum resistance.

## Key findings

- PDE1A overexpression correlates with advanced cancer stage, poor tumor grade, and platinum resistance in ovarian cancer.
- High PDE1A levels are an independent prognostic factor for worse disease-free and overall survival.
- PDE1A knockdown reduces cancer cell proliferation and β-catenin signaling, partially reversed by Wnt activators.

## Abstract

Phosphodiesterase 1A (PDE1A) regulates intracellular cyclic nucleotide signaling and has been implicated in tumor progression, but its clinical relevance and functional role in epithelial ovarian cancer (EOC), particularly in relation to the response to platinum remain unclear. This study aimed to evaluate the clinical significance of PDE1A in EOG and to clarify its functional role in tumor progression and response to platinum-based chemotherapy.

PDE1A mRNA and protein levels were analyzed using public databases, RNA sequencing, and immunohistochemistry. Correlations between PDE1A expression, clinicopathological features, and prognosis were assessed. Functional roles were investigated in ovarian cancer cell lines.

PDE1A was significantly overexpressed in EOC tissues compared with that in normal ovarian epithelial tissues. Overexpression correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, poor tumor grade, and reduced response to platinum-based chemotherapy. High PDE1A levels were linked to worse disease-free survival and overall survival, and multivariate analysis confirmed PDE1A as an independent prognostic factor. To elucidate its functional role, we performed in vitro experiments showing that PDE1A knockdown suppressed cell proliferation and colony formation, induced G1 arrest, and downregulated β-catenin signaling with reduced cyclin D1 and c-Myc expression. Notably, these inhibitory effects were partially rescued by lithium chloride (LiCl), a Wingless-related integration site (Wnt)/β-catenin activator.

In conclusion, our findings identify PDE1A as a Wnt/β-catenin–linked biomarker of tumor progression and platinum resistance in EOC and provide a biological rationale for further investigation of PDE1A-targeted strategies in preclinical models.