Determination of the prognostic value of HOXA9, HOXA11, NDRG2 and MGMT gene promoter methylation and clinical factors in glioblastoma patients

Glioblastoma is the most common and malignant primary brain tumor in adults. Despite advanced modes of treatment the survival time is still 12-14 months after diagnosis. Unfortunately, the etiology and pathogenesis of glioblastoma is not clear. Glioblastoma is the disease of multifactorial etiology which is influenced by external factors not so much as the body changes. Altered DNA methylation is one of the main type of epigenetic modifications in cancerous cells. Thus, the aim of the study was to evaluate the frequency of HOXA9, HOXA11, NDRG2, MGMT gene methylation in glioblastoma tumor tissue as well as to establish the effect of gene methylation and association between these genes with demographic and clinical factors on patients with glioblastoma survival. Glioblastoma is considered as the most aggressive and heterogeneous tumor, thus in this study we assessed frequency of some new epigenetic factors in tumor tissue and effect on patient survival and evaluated prognostic significance, which has not yet been studied. Additionally, we determined the frequency of MGMT gene promoter methylation in glioblastoma patient tumor tissue and the effect on survival in the relatively larger Lithuanian population. We also found the independent prognostic factors associated with longer or shorter overall survival in glioblastoma patients not only in groups of individual genes investigated and clinical factors but also in the relationship between these factor groups. In conclusion, this study indicated that gene methylation as well as demographic and clinical factors independently had the significant effect on overall survival in glioblastoma patients