title: An apoptotic molecular network identified by microarray: on the TRAIL to new insights in epithelial ovarian cancer.
abstract: BACKGROUND
  In a previous microarray expression analysis, the authors identified candidate genes that were expressed differentially between ovarian tumors with low malignant potential and invasive serous epithelial ovarian tumors. Among them, the apoptosis-related candidate genes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), caspase 8 (CASP8), FLICE-inhibitory protein (FLIP), and cytochrome C (CYC) were identified.
  
  
  METHODS
  For the current study, the authors conducted immunohistochemical analyses of a tissue array comprised of 235 serous tumors of different grades and stages to evaluate whether there was differential protein expression for these candidates and for the 4 death cell receptors of Trail: Dr4, Dr5, DcR1, and DcR2.
  
  
  RESULTS
  All proteins except DcR1 and DcR2 had significantly differential expression levels between grade 0 tumors (low malignant potential) and grade 2 and 3 tumors. Trail also showed differential expression between grade 0 tumors and grade 1 tumors. When all tumors were compared, the expression levels of Trail, Dr4, Dr5, DcR1, and Flip differed significantly between early-stage and advanced-stage disease. High Dr5 expression was associated with a poor prognosis in patients who had invasive tumors and in the subgroup of patients who had grade 3 tumors. Furthermore, the combinations of 2 proteins (Trail and Dr5, DcR2 and Cyc, Flip and Dr5, Flip and DcR2, DcR1 and Dr5 or Dr4 and Flip) revealed an association with patient prognosis.
  
  
  CONCLUSIONS
  The identification of new proteins in the initial diagnosis and prognosis of patients with epithelial ovarian cancer may lead to a better understanding of the disease, highlighting new potential therapeutic targets, and may be useful in patient management.
authors.affiliation: The Research Centre of the University of Montreal Teaching Hospital (CR-CHUM)/Montreal Cancer Institute, Montreal, Quebec, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Ouellet
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Page
authors.forename: Jason
authors.initials: J
authors.lastname: Madore
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guyot
authors.forename: Véronique
authors.initials: V
authors.lastname: Barrès
authors.forename: Christian
authors.initials: C
authors.lastname: Lussier
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
authors.forename: Diane M
authors.initials: DM
authors.lastname: Provencher
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000502:physiology*
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human