Methylation status and protein expression of RASSF1A in endometriosis

Oncology letters · 2016 · vol. 11(6) , pp. 4107–4112 · doi:10.3892/ol.2016.4512 · PMID:27313749 · W2344447853
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AI-generated summary by claude@2026-06, 2026-06-09

RASSF1A protein expression was reduced in endometriosis tissues, correlating with frequent promoter hypermethylation and epigenetic inactivation, suggesting a role in disease formation and progression.

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AI-generated deep summary by claude@2026-06, 2026-06-09

This study analyzed RASSF1A promoter methylation status and RASSF1A protein expression in ectopic and paired eutopic endometrium from 45 women with endometriosis, compared with normal endometrium from 20 women without endometriosis, using methylation-specific PCR and immunohistochemistry. RASSF1A protein was higher in the secretory phase of normal endometrium but was reduced in both ectopic and eutopic endometrium from women with endometriosis relative to normal controls, and RASSF1A promoter hypermethylation was detected in 55.56% of ectopic and 33.33% of paired eutopic samples but not in normal endometrium. The study reports that promoter hypermethylation was frequently associated with reduced RASSF1A expression and was common in advanced-stage ectopic lesions, with menstrual cycle phase accounted for between groups. A key limitation is that it is a tissue-based association study without functional experiments to establish causality. This paper is centrally about endometriosis — it specifically evaluates RASSF1A methylation and protein downregulation in ectopic and eutopic endometrium from women with endometriosis.

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Abstract

Ras association domain family 1A (RASSF1A) gene inactivation by promoter hypermethylation is a common event in the development of a variety of types of human cancer. Accumulated evidence has demonstrated that DNA methylation serve a critical role in the pathogenesis of endometriosis. The aim of the present study was to analyze the methylation status and protein expression of RASSF1A in endometriosis (EMS). The ectopic and corresponding eutopic endometrium tissues were collected from 45 women with EMS (EMS group) and normal endometrium tissues from 20 women without EMS (control group). The methylation status of RASSF1A was examined by methylation specific polymerase chain reaction (MSP). Immunohistochemistry was performed to measure RASSF1A protein level in endometrium tissues. In normal endometrium samples, RASSF1A protein expression was significantly higher at the secretory phase than the proliferative phase. RASSF1A protein expression in the ectopic endometrium tissues and eutopic endometrium tissues were significantly reduced than in normal endometrium (P<0.05). The frequency of aberrant methylation of RASSF1A was 55.56% in ectopic endometrium and 33.33% in paired eutopic endometrium, whereas such methylation was not detected in normal endometrium. Moreover, RASSF1A promoter hypermethylation was frequently associated with reduced expression of RASSF1A, and was common in advanced stage in ectopic endometrium of EMS. Epigenetic inactivation of RASSF1A through aberrant promoter methylation may be important in the formation and progression of EMS, and assessment of RASSF1A methylation status in eutopic endometrium may be a potentially useful biomarker to enhance the early detection of EMS.

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endometriosis

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