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2022-RA-630-ESGO Overexpression of PDEA1 is a predictive biomarker for platinum resistance and poor prognosis in epithelial ovarian cancer by regulating cell cycle
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  1. Gwan Hee Han1,
  2. Hee Yun2,
  3. Hyosun Kim3,
  4. Hanbyoul Cho3,
  5. Sunghoon Kim4 and
  6. Jae-Hoon Kim3
  1. 1Obststerics and gynecology, Kyung Hee University hospital at gangdong, Gangdong-gu, Korea, Republic of
  2. 2Gangnam Severance Hospital, Gangnam-gu, Korea, Republic of
  3. 3Yonsei University College of Medicine, Gangnam-gu, Korea, Republic of
  4. 4Yonsei University College of Medicine, Seodaemun-gu, Korea, Republic of

Abstract

Introduction/Background Phosphodiesterase 1A (PDE1A) belongs to a class of phosphohydrolytic enzymes that modulate the intensity of intracellular second messenger signaling and resulting in the integration of Ca2+ and cyclic nucleotide mediate in signaling in various disease such as cancers in expression and clinicopathological features, while its role its role in epithelial ovarian cancer (EOC) has not been clarified yet. Therefore, in this study we aim to evaluate the function, molecular mechanism and clinicopathological significance of PDE1A in EOC.

Methodology The qPCR, wester blotting and public data sets were used to evaluate the expression levle of PDE1A. Also, expression levels of PDE1A and clinicopathological characteristics were evaluated by immunohistochemistry staining of EOC, borderline, benign and normal epithlelial tissues. Its functional role and association with cell cycle were evaluated in EOC cell lines.

Results High mRNA and protein levels of PDE1A were observed in EOCs compared to borderline, benign and normal nonadjacent ovarian epithelial tissues (p < 0.001). Also, high expression of PDE1A was significantly associated with serous (p = 0.023), high grade (p = 0.012), advanced stage FIGO stage (p < 0.001), and resistance to platinum based chemotherapy (p < 0.001) EOCs. Importantly, high expression level of PDE1A was indicated as a prognosis predictive biomarker by Cox mulrivariate analysis. Specifically, we observed that PDE1Apromoted G2/M transition by regulating cyclin B1 trascription.

Conclusion Taken together, our findings suggested that PDEA1A is a promosing biomarker for prediction of progosnosis and resistance to platinum based chemotherapy in EOC patients.

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