title: Prognostic significance of EDN/RB, HJURP, p60/CAF-1 and PDLI4, four new markers in high-grade gliomas.
abstract: BACKGROUND
  Recent studies have highlighted the heterogeneity of gliomas and demonstrated that molecular and genetic analysis could help in their classification and in the design of treatment protocols. In a previous study we have identified a 4-gene signature highly correlated with survival of glioma patients. The aim of this study is to confirm and extend these findings by investigating the expression of these genes at the protein level and their association with outcome of patients with high grade gliomas.
  
  
  RESULTS
  Immunohistochemical staining for EDN/RB, HJURP, p60/CAF-1 and PDLI4 was studied on archive materials from 96 patients (64 glioblastomas and 32 grade III gliomas). The levels of all four proteins differed significantly between grade III and grade IV tumours. The levels of the EDN/RB, HJURP and p60/CAF-1 proteins were strongly associated with overall survival (p<0.001, p<0.001 and p=0.002, respectively), whereas the one of PDLI4 was not (P=0.11). A risk criterion defined as high levels of at least two of the EDN/RB, HJURP and p60/CAF-1 proteins accurately predicted the prognosis of patients. Multivariate analysis confirmed that this criterion was an independent negative prognostic marker (hazard ratio = 2.225; 95% CI, 1.248 to 3.966, p=0.007).
  
  
  CONCLUSIONS
  The expression of the EDN/RB, HJURP, p60/CAF-1 and PDLI4 proteins is disrupted in high grade gliomas and increases in the levels of these proteins are closely linked to tumour aggressiveness and poor outcome.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Unité mixte de recherche - UMR 6290, Institut Génétique et Développement de Rennes, Rennes, France ; Université Rennes 1, UEB - Université européenne de Bretagne, Biosit, Faculté de Médecine, Rennes, France ; CHU - Centre Hospitalier universitaire de Rennes, Service de Génétique Moléculaire et Génomique, Rennes, France.
authors.forename: Marie
authors.initials: M
authors.lastname: de Tayrac
authors.forename: Stephan
authors.initials: S
authors.lastname: Saikali
authors.forename: Marc
authors.initials: M
authors.lastname: Aubry
authors.forename: Pascale
authors.initials: P
authors.lastname: Bellaud
authors.forename: Rachel
authors.initials: R
authors.lastname: Boniface
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
authors.forename: Jean
authors.initials: J
authors.lastname: Mosser
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology; D056504:Chromatin Assembly Factor-1 / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000175:diagnosis* / Q000473:pathology; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins / Q000032:analysis*; D009367:Neoplasm Staging; D011379:Prognosis; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C533593:CHAF1B protein, human; D056504:Chromatin Assembly Factor-1; D004268:DNA-Binding Proteins; C000588596:EDNRB protein, human; C524371:HJURP protein, human; D060588:LIM Domain Proteins; C486247:PDLIM4 protein, human; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin
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