TRAIL-R3 -related apoptosis: Epigenetic and expression analyses in women with ovarian neoplasia

• Published in: Gynecologic oncology Vol. 126; no. 2; pp. 268 - 273
• Main Authors: Braga, Letícia da Conceição, Álvares da Silva Ramos, Ana Paula, Traiman, Paulo, Silva, Luciana Maria, Lopes da Silva-Filho, Agnaldo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2012
• Subjects: Apoptosis - physiology; Cell Line, Tumor; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - metabolism; Cystadenocarcinoma, Serous - pathology; Decoy receptor; Disease-Free Survival; DNA Methylation; Epigenomics; Female; Gene expression; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins - biosynthesis; GPI-Linked Proteins - genetics; Hematology, Oncology and Palliative Medicine; Humans; Methylation; Middle Aged; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Prospective Studies; Receptors, Tumor Necrosis Factor, Member 10c; TRAIL-R3; Tumor Necrosis Factor Decoy Receptors - biosynthesis; Tumor Necrosis Factor Decoy Receptors - genetics; Decoy receptor; TRAIL-R3; Gene expression; Methylation; Ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2012.04.038

Abstract Objective To assess the expression of TRAIL - R3 and the methylation of a CpG island within the TRAIL-R3 promoter both in cystadenoma tumors and primary and metastatic epithelial ovarian carcinoma (EOC). Methods RNA was obtained from women with normal ovarian (NO) tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and EOC (n = 16) using Trizol®. Quantitative PCR (qRT-PCR) was performed to quantify the relative levels of TRAIL-R3 . The methylation frequency of the CpG island in the TRAIL-R3 promoter was assessed using the methylation-specific PCR (MSP) assay after DNA bisulfite conversion. The differences between the groups were evaluated using the chi-square, Student's t, ANOVA, Mann–Whitney U, Wilcoxon or Kruskal–Wallis tests as indicated. The survival rates were calculated using the Kaplan–Meier method. Results Cystadenoma and metastatic EOC tumors expressed significantly more TRAIL-R3 mRNA than primary EOC tumors. Methylation of the TRAIL-R3 promoter was absent in NO tissues, while hemimethylation of the TRAIL-R3 promoter was frequently found in the neoplasia samples with 45.4% of the cystadenoma tumors, 8.3% of the primary EOC samples and 11.1% of the metastatic EOC samples showing at least partial methylation (p = 0.018). Neither the expression of TRAIL-R3 nor alterations in the methylation profile were associated to cumulative progression-free survival or the overall survival in EOC patients. Conclusions Primary EOC is associated to a lower TRAIL-R3 expression, which leads to a better understanding of the complex disease and highlighting potential therapeutic targets. Promoter DNA methylation was not related to this finding, suggesting the presence of other mechanisms to transcriptional control.