Журнал онкологических исследований и лечения

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Determination of the Cutoff Point of the Absolute Value of MGMT mRNA for Predicting the Therapeutic Resistance to Temozolomide in Glioblastoma

Satoshi Tanaka, Jiro Akimoto and Yoshitaka Narita

Abstract Purpose: In our previous study we have reported the absolute value of O6-methylguanine-DNA methyltransferase (MGMT) messenger RNA (mRNA) which was acquired by using real-time reverse transcription polymerase chain reaction (RT-PCR). Probably the value may be useful for envisioning both the prognosis and the outcomes of the therapy for glioblastoma (GB) treated by Temozolomide (TMZ). Methods: MGMT mRNA was studied in 55 newly diagnosed cases of GB treated with TMZ and radiation (with less than 75 y and had a Karnofsky performance status (KPS) of at least 60), based upon the technique of realtime reverse transcription polymerase chain reaction (RT-PCR) using the TaqMan probe. A receiver operating characteristic analysis was carried out in order to determine the cutoff points for progression free survival (PFS) as well as overall survival (OS). Results: In 55 patients with GB, 1200 and 3600 for PFS (specificities of 88.9 and 66.7%, and sensitivities of 36.7 and 50.0%, respectively); 1200, 2100 and 2900 copies/μg RNA for OS (specificities of 83.6, 73.9 and 69.6%, and sensitivities of 39.1, 47.8 and 52.2%, respectively) were the candidate cutoff points. Significantly longer PFS and OS were observed in patients who did not exceed 1200 copies/μg RNA (p=0.0035 for PFS and 0.0189 for OS by logrank test). Median overall survival of the GB patients who had less than 1200 copies/μg RNA treated with TMZ and radiation was 36 months. Conclusion: One Thousand and two hundreds copies/μg RNA appeared to be the most reasonable cutoff point of MGMT mRNA in GB for deciding to use other anti-tumor drugs such as Bevacizumab together with TMZ.