Promoter Methylation of RASSF1A Gene in Egyptian Patients with Ovarian Cancer

Abstract

Ovarian malignancy is diagnosed in nearly a fourth of a million women internationally every year. Methylation of RASSF1A tumor suppressor gene prompts its inactivation in diseases. In this study, the RASSF1A promoter methylation was detected by methylated-specific PCR and investigated serum RASSF1A protein level through enzyme-linked immunosorbant assay in 160 Egyptian patients with ovarian cancer and 160 healthy controls. The present work proved that there was a higher frequency of RASSF1A methylation and a decrease in its serum level in patients with ovarian cancer compared to controls as well as in the high-grade tumor patients compared to low grade ones and also in advanced ovarian tumor stage compared to early stages. Our study exhibited that RASSF1A promoter hypermethylation and its protein levels may be a reliable and sensitive tool for diagnosing and monitoring of ovarian malignancy patients.

Development and Validation of a Prognostic Nomogram Based on DNA Methylation-Driven Genes for Patients With Ovarian Cancer

“…Dysregulated DNA methylation-related genes can promote malignant transformation through the silencing of TSGs or overexpression of oncogenes, which constitutes a new balance in the tumor microenvironment and may become a predictive biomarker of prognosis. TSGs usually show promoter hypermethylation and inhibit its expression, thereby promoting the pathogenesis of OC ( Chen et al, 2018 ; Rezk et al, 2018 ). The promoter of TSGs ( BRCA1 and RASSF1A ) is hypermethylated in OC tissues ( Ibanez de Caceres et al, 2004 ).…”

“…The promoter of TSGs ( BRCA1 and RASSF1A ) is hypermethylated in OC tissues ( Ibanez de Caceres et al, 2004 ). Hypermethylation silences expression to inhibit BRCA1 function, driving genomic instability in OC ( Rezk et al, 2018 ). Silencing of RASSF1A promotes cell cycle progression and uncontrolled cell growth.…”

Current data and future perspectives on DNA methylation in ovarian cancer (Review)

“…According to recent research, RASSF1A methylation is increased in OC compared with normal ovarian tissues ( 60 ). Furthermore, the methylation frequency of RASSF1A has been found to be higher in patients with HGSOC ( 61 ). Additionally, the methylation frequency of RASSF1A was higher in OC than in low malignant potential tumors, which exhibited higher methylation levels of RASSF1A than benign ovarian epithelial adenomas ( 62 ).…”

“…As previously described by Belsky et al (192), the DNA methylation of related genes can be used as a biomarker to predict the rate of aging. Previous studies on DNA methylation in OC have provided critical evidence for understanding ovarian tumorigenesis (61)(62)(63)(64). These findings provide potential diagnostic biomarkers and therapeutic targets.…”

Dietary Compounds as Epigenetic Modulating Agents in Cancer

“…The hypermethylation of RASSF1A gene has been identified as a diagnostic marker in lung cancer, whereas it contributes to increased mortality in women with breast cancer. Hypermethylation of RASSF1A also has been related with high risk of ovarian cancer (El-Sherif et al, 2016; Rezk et al, 2018; Yadav et al, 2018). Other studies showed that hypermethylation of PDE3A gene modulated the response to therapy in cisplatin-resistant non-small cell lung cancer (NSCLC) (Tian et al, 2017).…”