title: NDRG2 and NDRG4 Expression Is Altered in Glioblastoma and Influences Survival in Patients with MGMT-methylated Tumors.
abstract: OBJECTIVE
  The N-myc down-regulated gene (NDRG) family is a group of genes that have predominantly tumor-suppressive effects. The goal of this study was to investigate the expression of NDRG2 and NDRG4 in surgical specimens of human glioblastoma and in normal brain tissue, and to search for correlations with overall (OS) and progression-free survival (PFS).
  
  
  METHODS
  Samples from 44 patients (31 males, 13 females; mean age±SD=57.4±15.7 years) with primary (n=40) or recurrent glioblastoma (n=4) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry, with dimensionless semiquantitative immunoreactivity score (IRS), ranging from 0-30] for expression of NDRG2 and NDRG4. Five non-tumorous autopsy brain specimens were used as controls.
  
  
  RESULTS
  On the protein level, expression of NDRG2 was significantly down-regulated in glioblastoma (IRS=3.5±3.0 vs. 8.8±3.3; p=0.001), while expression of NDRG4 was significantly up-regulated (IRS=5.4±3.7 vs. 0.75±0.4 vs, p<0.001). There was no statistically significant difference in PFS between a group of 15 patients with glioblastoma with MGMT methylation and enhanced expression of NDRG4 mRNA who were treated with adjuvant radiochemotherapy (temozolomide and 60 Gy) and a group of patients with low expression of NDRG4 mRNA [10 (range=5.5-14.2) months vs. 21 (range=10.7-31.3) months] (p=0.13).
  
  
  CONCLUSIONS
  Expression of both NDRG2 and NDRG4 genes is significantly altered in glioblastomas. PFS among the patients with glioblastoma with MGMT methylation treated with radiochemotherapy differed significantly in high-expression groups compared to patients without MGMT methlation and without radiochemotherapy (p<0.05).
authors.affiliation: Department of Neurosurgery, Justus Liebig University, Giessen, Germany malgorzata.kolodziej@neuro.med.uni-giessen.de.
authors.forename: Malgorzata A
authors.initials: MA
authors.lastname: Kolodziej
authors.affiliation: Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weischer
authors.affiliation: Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
authors.forename: Marcus H T
authors.initials: MH
authors.lastname: Reinges
authors.affiliation: Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Uhl
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Schwarm
authors.affiliation: Department of Neuropathology, Justus Liebig University, Giessen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Schänzer
authors.affiliation: Department of Neuropathology, Justus Liebig University, Giessen, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Acker
authors.affiliation: Department of Neuropathology, Erlangen University Hospital, Erlangen, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Quint
authors.affiliation: Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
authors.affiliation: Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Stein
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; C466228:NDRG2 protein, human; C431705:NDRG4 protein, human; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: Glioblastoma multiforme; MGMT methylation; NDRG2; NDRG4; patient survival