Methylation status and protein expression of RASSF1A in endometriosis

Abstract

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.

Role of Oxidative Stress in Epigenetic Modification in Endometriosis

“…The present study summarizes the genome-wide methylation profile of endometriosis. 17,20,21,27,30,33,39,44,46,47,51,54,[75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93] Many studies have reported abnormal methylation patterns of selected genes in endometriotic lesions and endometria of patients with endometriosis. We found peer-reviewed research articles published about the association of DNA methylation with endometriosis.…”

DNA methylation alterations—potential cause of endometriosis pathogenesis or a reflection of tissue heterogeneity?†

“…Highly heterogeneous endometriotic lesions, which are removed during laparoscopic surgery, have been an attractive study object for both candidate gene-based and genome-wide DNA methylation studies [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Up to date, DNA methylation profiles of more than 10 candidate genes and transposable element involved in different pathways, such as hormonal signalling (PGR, ESR1, ESR2, COX-2, COMT), ovarian cancer progression (LINE-1), carcinogenesis (PAX2), tumour repressor and apoptosis-related genes (CDH1, RASSF), tissue remodelling (MMP2, MMP3, MMP7, TIMP3 and TIMP4) and genes needed for endometrial growth, differentiation, and implantation (HOXA10) have been investigated and associated with disease pathogenesis in whole endometriotic lesion biopsies (Table 1).…”

“…The candidate gene-based and DNA microarray studies comparing endometria from women with and without endometriosis have brought out number of disease related genes (Table 2) [12,15,16,18,19,[33][34][35][36][37][38][39][40][41][42]. The candidate gene-based studies have reported dysregulation of genes involved in many important biological functions, such as hormonal regulation (COX-2), development of female genital tract (PAX2), endometrial growth and receptivity (HOXA10, HOXA11) and tumor suppression (RUNX3, RASSF1A, CDH1) [12,33,34,36,38,39,43,44].…”