title: 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 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.
authors.affiliation: Cell Biology Laboratory of Research and Development Management of Ezequiel Dias Foundation, Belo Horizonte, MG, Brazil.
authors.forename: Letícia da Conceição
authors.initials: Lda C
authors.lastname: Braga
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Alvares da Silva Ramos
authors.forename: Paulo
authors.initials: P
authors.lastname: Traiman
authors.forename: Luciana Maria
authors.initials: LM
authors.lastname: Silva
authors.forename: Agnaldo
authors.initials: A
authors.lastname: Lopes da Silva-Filho
mesh_terms: D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D018572:Disease-Free Survival; D057890:Epigenomics; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053319:Tumor Necrosis Factor Decoy Receptors / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D058851:GPI-Linked Proteins; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C108661:TNFRSF10C protein, human; D053319:Tumor Necrosis Factor Decoy Receptors