TRAIL-R3 -related apoptosis: Epigenetic and expression analyses in women with ovarian neoplasia
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...
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Published in | Gynecologic oncology Vol. 126; no. 2; pp. 268 - 273 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.08.2012
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Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0090-8258 1095-6859 |
DOI: | 10.1016/j.ygyno.2012.04.038 |