LOW MGMT EXPRESSION BY NANOSTRING IS ASSOCIATED WITH BETTER OUTCOME OF TMZ-TREATED GLIOBLASTOMA PATIENTS

Glioblastoma (GBM) is the deadliest primary malignant brain tumor in adults with a median 5-year overall survival of 6.8%. Primary GBM accounts for 90% of cases, which arises “de novo and lack mutations in IDH genes (IDH^WT), while secondary GBM arises from a malignant progression from low-grade gliomas with mutations in IDH genes (IDH^MUT). The standard treatment for GBM consists of surgery, radiotherapy, and temozolomide (TMZ). TMZ treatment response is heterogeneous, and MGMT promoter (MGMTp) methylation status has been the major predictive biomarker. Herein, we described the clinical and molecular data of TMZ-treated GBM patients and we analyzed the correlation between MGMT methylation with MGMT gene expression as well as patients outcome. Samples from adult GBM patients (n=112; IDH1^WT: n=96; IDH1^MUT: n=16) treated with TMZ according to Stupp protocol at Barretos Cancer Hospital, SP, Brazil, were analyzed. Positive ATRX expression was found in 91.6% (88/96) of IDH^WT and 47.0% (8/17) of IDH^MUT. TERTp mutations were detected in 70.4% (50/71) of IDH^WT: and 11.1% (1/9) of IDH^MUT. The MGMTp methylation was found in 55.5% (35/63) of IDH^WT and 85.7% (12/14) of IDH^MUT, and as expected, the MGMTp methylation was correlated with a better response to TMZ (p=0.0001) and was inversely correlated with MGMT mRNA levels (-0.506, p <0.0001). High levels of MGMT mRNA was associated with poor patient survival. In the present study, we first identified that the MGMT mRNA levels evaluated by NanoString were associated outcome of TMZ-treated glioblastoma patients. The combination of MGMT methylation and mRNA expression may provide more accurate results regarding prediction of TMZ response in glioblastoma patients.