Hypermethylation of P₁₅, P₁₆, and E-cadherin genes in ovarian cancer

Abstract

Both p16 and p15 proteins are inhibitors of cyclin-dependent kinases that prevent the cell going through the G1/S phase transaction. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells. Two groups of patients were selected: the first group suffered from epithelial serous ovarian tumors and the second group suffered from benign ovarian lesions; ovarian tissue samples from all the subjects (benign and malignant) were subjected to methylation-specific polymerase chain reaction for methylated and unmethylated alleles of the genes (E-cadherin, p15, and p16). Results obtained showed that aberrant methylation of p15 and p16 genes were detected in 64.29 and 50% of ovarian cancer patients, while E-cadherin hypermethylation was detected in 78.57% of ovarian cancer patients. Methylation of E-cadherin was significantly correlated with different stage of disease (p < 0.05). It was found that the risk of E-cadherin hypermethylation was 1.347-fold, while risk of p15 hypermethylation was 1.543-fold and p16 was 1.2-fold among patients with ovarian cancer than that among patients with benign ovarian lesions. In conclusion, Dysfunction of the cell cycle and/or the cell-cell adhesion molecule plays a role in the pathogenesis of ovarian cancer and that the analysis of the methylation of p15 and E-cadherin genes can provide clinically important evidence on which to base the treatment.

DNA methylation profiles in ovarian cancer: Implication in diagnosis and therapy (Review)

“…Genes involved in cell cycle pathways such as p16 and p15 have also been affected by altered methylation of their promoters (48). E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells.…”

Quantitative assessment of aberrant <em>P16^INK4a</em> methylation in ovarian cancer: a meta-analysis based on literature and TCGA datasets

“…After reading titles and abstracts, 84 records were identified for further full-text assessment, which further excluded 60 more articles. Finally, 24 studies from 1997 to 2015 were included in this meta-analysis 17,20,22–30,37–49…”

“…The detection methods of methylation in 20 studies were methylation-specific PCR (MSP) and real-time quantitative MSP, while methylation-specific multiplex ligation-dependent probe amplification was used in two studies, MethyLight was used in one study, and Southern analysis was used in one study. Among the 24 articles, 20 studies17,20,22–30,37–40,42,45–47,49 addressed the risk of P16 INK4a promoter methylation in ovarian cancer, 10 studies20,25,28,29,38,41,43,44,47,48 covered clinicopathological features, and 3 studies20,42,43 discussed prognosis. To explore the relationship between P16 INK4a promoter methylation and ovarian cancer risk, three groups, that is, normal tissues, benign tissues, and low malignant potential or borderline tumor tissues (LMP), were compared.…”

“…Also, P16 INK4a inactivation upregulates retinoblastoma (RB) protein by stimulating the cyclin-dependent kinases (CDKs) and RB pathway, which leads to dysfunction of cell proliferation and apoptosis, thereby further facilitating carcinogenesis 16. Indeed, several types of cancer, including ovarian cancer, exhibit a methylation phenotype of P16 INK4a 17–19…”

Indole Derivative Interacts with Estrogen Receptor Beta and Inhibits Human Ovarian Cancer Cell Growth

“…In addition, CDKN2A inactivation upregulates RB, stimulating the cyclin-dependent kinases (CDKs) and the RB pathway, which leads to malfunction of cell proliferation and apoptosis, thereby further facilitating carcinogenesis [ 36 ]. Indeed, several types of cancer, including ovarian cancer, exhibit a methylation phenotype of CDKN2A [ 37 , 38 , 39 ]. Interestingly, other authors have suggested that aberrant methylation of CDKN2A promoter may be essential to the initiation of ovarian cancer and in distinguishing malignant from healthy ovarian tissues.…”