Epigenetic Characteristics in Primary and Recurrent Glioblastoma-Influence on the Clinical Course.

OBJECTIVE

Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value.

METHODS

A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of , , and methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results.

RESULTS

Instability was observed in all examined epigenetic markers. methylation changed in 30% of patients, methylation changed in 35%, and methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results.

CONCLUSIONS

Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.