Is the absolute value of O6-methylguanine-DNA methyltransferase gene messenger RNA a prognostic factor, and does it predict the results of treatment of glioblastoma with temozolomide?

Aug 9, 2014Journal of neurosurgery

Can the level of a specific DNA repair gene's messenger RNA predict outcomes and treatment response in glioblastoma patients treated with temozolomide?

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Abstract

The mean MGMT mRNA value was significantly lower in oligodendroglial tumors than in other tumors.

In 73 GBMs, fewer than 1000 copies/μgRNA of MGMT mRNA is associated with a significant increase in progression-free survival (p = 0.0150).
Among 45 patients with GBMs treated with temozolomide and radiation, those with fewer than 1000 copies/μgRNA of MGMT mRNA had significantly longer progression-free survival compared to those with more than 1000 copies/μgRNA (p = 0.0090).
For 32 patients younger than 75 years with a Karnofsky Performance Scale score over 70, fewer than 5000 copies/μgRNA of MGMT mRNA is linked to longer progression-free and overall survival times (p = 0.0365 and p = 0.0312).
Quantification of MGMT mRNA may be useful for predicting therapeutic outcomes in patients with GBMs treated by temozolomide.

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OBJECTIVES: Methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) has been reported to be a good prognostic factor for patients with glioblastoma multiforme (GBM). To determine whether the absolute value of MGMT messenger RNA (mRNA) might be a prognostic factor and useful for predicting the therapeutic effectiveness of temozolomide, especially with regard to GBMs, the authors measured the absolute value of MGMT mRNA in gliomas by using real-time reverse-transcription polymerase chain reaction (RT-PCR).

METHODS: MGMT mRNA was measured in 140 newly diagnosed gliomas by real-time RT-PCR using the Taq-Man probe. Among 73 GBMs, 45 had been initially treated with temozolomide and radiation.

RESULTS: The mean MGMT mRNA value was significantly lower in oligodendroglial tumors than in other tumors. In the 73 GBMs, a significant prognostic factor for progression-free survival was fewer than 1000 copies/ μgRNA of MGMT mRNA (p = 0.0150). Of 45 patients with GBMs that had been treated with temozolomide and radiation, progression-free survival was significantly longer for those whose GMB had fewer than 1000 copies/μgRNA of MGMT mRNA than for those whose GBM had more than 1000 copies/μgRNA (p = 0.0090). In 32 patients with GBMs treated by temozolomide and radiation whose age was younger than 75 years and whose Karnofsky Performance Scale score was more than 70, progression-free and overall survival times were longer for those with GBMs of fewer than 5000 copies/μgRNA of MGMT mRNA than for those with GBMs of more than 5000 copies/μgRNA (p = 0.0365 and p = 0.0312).

CONCLUSIONS: MGMT mRNA might be useful as a prognostic factor and for predicting the results of therapy for GBMs treated by temozolomide. New individual adjuvant therapy based on the results of MGMT mRNA quantitation has been proposed.

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Is the absolute value of O6-methylguanine-DNA methyltransferase gene messenger RNA a prognostic factor, and does it predict the results of treatment of glioblastoma with temozolomide?

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