Prognostic value of H-MLH1 after adjusting for RPA class in GBM patients

Abstract

Repair of DNA adducts appears to be an important mechanism in chemotherapy responsiveness in glioblastoma multiforme (GBM). Meta-analyses have suggested that the addition of chemotherapy increases the percentage of long-term survivors. Because GBM is characterized by multiplicity of pathways that characterize growth and treatment resistance, we hypothesized probing a multiplicity of repair factors may be able to identify more than one prognostic factor that may be utilized in molecularly targeted therapy that might improve survival and QOL. Seven DNA repair factors showed statistical significance when added to the initial logistic model of RPA class on length of survival status. After adjusting for RPA class the only statistically significant result of the multivariable logistic regressions for these 7 DNA repair factors was that as hMLH1-MF1 increased, the odds of being a short-term survivor versus a long-term survivor decreased (OR: 0.913, 95 per cent CI: 0.838-0.995, p=0.0385), multivariable analysis showed no associations between survival status and MGMT and p53 status, and the only statistically significant prognostic DNA repair factor was human Mut L Homologue 1 (hMLH1).