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ARTICLE

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

Gwan Hee Han^1,2,#, Hee Yun^3,#, Joon-Yong Chung⁴, Jae-Hoon Kim^3,5,6, Hanbyoul Cho^3,5,6,*

1 Department of Obstetrics and Gynecology, Chung-Ang University College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea
2 Department of Obstetrics and Gynecology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul, 06973, Republic of Korea
3 Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Gangnam-gu, Seoul, 06299, Republic of Korea
4 Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
5 Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, 06299, Republic of Korea
6 Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

* Corresponding Author: Hanbyoul Cho. Email:
# These authors contributed equally to this work and are the first coauthors of this work

(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research 2026, 34(3), 16 https://doi.org/10.32604/or.2025.072105

Received 19 August 2025; Accepted 12 December 2025; Issue published 24 February 2026

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

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Supplementary Material

Supplementary Material File

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