RUNX3 is inactivated by promoter hypermethylation in malignant transformation of ovarian endometriosis
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RUNX3 inactivation by promoter hypermethylation is increased in malignant ovarian endometriosis and linked to ERα expression, suggesting a role in malignant transformation.
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Abstract
The aim of the present study was to investigate the role of epigenetic inactivation of the runt-related transcription factor 3 gene (RUNX3) in the malignant transformation of ovarian endometriosis. Samples obtained by microdissection and scraping included 30 malignant ovarian endometriotic cyst tissues and 30 corresponding eutopic endometrium tissues from the endometriosis-associated ovarian carcinoma (EAOC) group, 19 benign ovarian endometriotic cyst tissues and 22 corresponding eutopic endometrium tissues from the endometriosis (EM) group and 22 normal eutopic endometrium tissues from the control endometrium (CE) group. RUNX3 methylation status was determined by methylation-specific PCR and bisulfite sequencing, while levels of RUNX3 and ERα protein expression were evaluated using immunohistochemistry. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the malignant ovarian endometriotic cysts from the EAOC group was significantly higher than that in the benign ovarian endometriotic cysts from the EM group. The percentage of RUNX3 methylation and negative RUNX3 protein expression in the eutopic endometrium from the EAOC group was significantly higher than that in the EM and CE groups. An inverse correlation between positive RUNX3 protein expression and methylation was observed and a positive correlation was shown between RUNX3 methylation and ERα protein expression. In the malignant ovarian endometriotic cysts from the EAOC group, there was no significant correlation between methylation frequency of the RUNX3 gene and histological type. However, the percentage of RUNX3 gene methylation was significantly higher in the tissue samples from patients with surgical stage IC EAOC than the percentage in patients with stage IA and IB disease. These results suggest that RUNX3 inactivation by promoter hypermethylation plays a role in the progression of malignant transformation of ovarian EM and is closely related to estrogen metabolism. Negative protein expression and abnormal RUNX3 methylation in the eutopic endometrium could be used as diagnostic markers in patients with ovarian EM who may be at an increased risk of developing EAOC.
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Cited by (13)
- Fibroblast heterogeneity and FN1-mediated signaling in endometriosis revealed by single-cell and spatial transcriptomics 2025
- A systematic review of epigenetics of endometriosis 2024
- Correlation of clinicopathological and prognostic characteristics between endometriosis-associated and primary ovarian cancer 2023
- Endometriosis Stem Cells as a Possible Main Target for Carcinogenesis of Endometriosis-Associated Ovarian Cancer (EAOC) 2022
- Oestrogen up-regulates DNMT1 and leads to the hypermethylation of RUNX3 in the malignant transformation of ovarian endometriosis 2021
- Correlation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary Ovarian Cancer 2021
- Endometriosis and endometriosis associated ovarian cancer 2021
- Endometriosis-associated ovarian cancer: What have we learned so far? 2019
- Endometriosis Malignant Transformation: Epigenetics as a Probable Mechanism in Ovarian Tumorigenesis 2018
- Epigenetics in Human Reproduction and Gynecologic Diseases 2018
- DNA methylation alterations—potential cause of endometriosis pathogenesis or a reflection of tissue heterogeneity?† 2018
- Endometriosis and Ovarian Cancer: an Integrative Review (Endometriosis and Ovarian Cancer) 2017
- DNA methylation in endometriosis (Review) 2016
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- europepmc
- last seen: 2026-06-04T01:30:01.192114+00:00
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- last seen: 2026-06-10T17:14:06.276822+00:00
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