Mesenchymal subtype of glioblastomas with high DNA-PKcs expression is associated with better response to radiotherapy and temozolomide.

A better understanding of the relationship between glioblastomas molecular subtypes and radio-chemotherapy is needed for the development of individualized strategies. In this study, we aimed to assess whether non-homologous end-joining (NHEJ) protein expression is associated and could predict responses to treatment of mesenchymal (MES) and proneural (PN) subtypes. Tumors from 122 patients with a glioblastoma treated at the University Hospital of Poitiers between 2002-2013 by an association of radiotherapy and temozolomide were collected. Among these tumors, 80 were suitable for in situ analysis and were included in TissueMicroArray. The expression of DNA-PKcs, Ku70, Ku80 and CD44, Olig2 (respectively surrogate markers of MES and PN subtypes) were evaluated by immunohistochemistry. The median survival of patients with high and low CD44 expression was 11.9 months (95% CI 7.7-14) and 19.1 months (95% CI 15.2-22.4) respectively (p = 0.008). Median survival of patients with high and low DNA-PKcs levels was 20.0 months (95% CI 15.2-25.3) and 12.9 months (95% CI 9.9-19.5) respectively (p = 0.036). High levels of Olig2, Ku70 and Ku80 tended to be associated with better overall survival but no significant differences were found. Overall survival of class I patients (CD44+ and DNA-PKcs+) was longer than class II (CD44+ and DNA-PKcs- or CD44- and DNA-PKcs+) and class III (CD44- and DNA-PKcs-), (p = 0.005 and 0.003 respectively). High levels of CD44 and DNA-PK are associated with a better survival and better response to radiotherapy and temozolomide and could establish prognosis classes by predicting survival and response to therapy for GBMs patients.