Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme.

PURPOSE

To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy.

MATERIALS AND 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).

CONCLUSION

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.