title: Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme.
abstract: OBJECTIVE
  To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy.
  
  
  METHODS
  Thirty four patients with GBM received postoperative radiotherapy. Tumor sections were examined for poly-ADP ribose polymerase-1 (PARP-1) and DNA protein kinase (DNA-PK) expression. Immunohistochemical staining intensities of PARP-1 and DNA-PK were determined (score 0-3) and expression levels were correlated with patients overall survival.
  
  
  RESULTS
  Median survival time of the whole study group was 10.0 months (95% CI 8.1-11.9). Median survival of patients with high and low (≥median and <median) tumor PARP-1 levels were 10.0 months (95% CI 7.9-12.1) and 12.0 months (95% CI 8.3-15.7), respectively (p=0.93). In contrast, median survival of patients with high and low tumor DNA-PK levels were 9.0 months (95% CI 7.2-10.8) and 13.0 months (95% CI 10.7-15.3), respectively (p=0.02). In multivariate analysis, DNA-PK expression emerged as a significant independent predictor for overall survival (HR 3.9, 95% CI 1.5-10.7, p=0.01).
  
  
  CONCLUSIONS
  This hypothesis generating study showed that high tumor levels of DNA-PK correlate with poor survival of GBM patients. Further studies are needed to confirm these results and to clarify whether DNA-PK inhibitors might have a potential to radiosensitize GBM and improve the treatment outcome of this devastating disease.
authors.affiliation: Department of Radiotherapy, North Estonia Medical Centre, Tallinn, Estonia.
authors.forename: Marju
authors.initials: M
authors.lastname: Kase
authors.forename: Markus
authors.initials: M
authors.lastname: Vardja
authors.forename: Agu
authors.initials: A
authors.lastname: Lipping
authors.forename: Toomas
authors.initials: T
authors.lastname: Asser
authors.forename: Jana
authors.initials: J
authors.lastname: Jaal
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D019635:Neurosurgical Procedures / Q000379:methods; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D011065:Poly(ADP-ribose) Polymerases