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Predictive markers for MGMT promoter methylation in glioblastomas

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Abstract

The promoter methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene has been described as the most important predictor of chemotherapeutic response and patients’ survival in glioblastomas (GBs). Therefore, prediction of the MGMT promoter methylation status by imaging would help to preoperatively decide the overall treatment strategy as well as surgical strategy. This study aimed to detect imaging parameters to predict MGMT promoter methylation in GBs by using a commercially available software. We investigated three imaging features (ring enhancement, tumor location, and laterality) and apparent diffusion coefficient (ADC) parameters in 48 newly diagnosed GBs treated at Keio University Hospital in 2006 or later. For ADC, texture analyses were performed. Regions of interest (ROIs) were drawn manually with reference to contrast-enhanced areas, excluding necrotic and cystic regions. Mean ADC value and ADC histogram parameters, including kurtosis, skewness, and entropy, were compared with MGMT promoter methylation. Each parameter was evaluated to determine correlation with MGMT promoter methylation, and the parameters with significant associations with the methylation status were correlated with the MGMT-positive cell ratio determined by immunohistochemistry (IHC) analysis. The mean ADC value and ADC entropy were significantly associated with MGMT promoter methylation. The combination of mean ADC value and ADC entropy predicted MGMT promoter methylation, with a PPV of 81.2% and specificity of 88.9%. The mean ADC value and ADC entropy were negatively correlated with the MGMT-positive cell ratio in the IHC analysis. This study demonstrated that texture analyses of ADC histograms in GBs were predictive of MGMT promoter methylation.

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Acknowledgements

We greatly thank Ms. Naoko Tsuzaki at the Department of Neurosurgery, Keio University School of Medicine for technical assistance of laboratory works. The authors also greatly thank Dr. Takayuki Abe at the Center for Clinical Research, Department of Preventive Medicine and Public Health, Keio University School of Medicine for statistical advice.

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Correspondence to Tokunori Kanazawa.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of Keio University. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Fig. S2
figure4

ROC curve for MGMT promoter methylation status correlated with the mean ADC value (PNG 84 kb)

Fig. S3
figure5

ROC curve for MGMT promoter methylation status correlated with ADC entropy (PNG 105 kb)

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High resolution image (TIF 140 kb)

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Kanazawa, T., Minami, Y., Jinzaki, M. et al. Predictive markers for MGMT promoter methylation in glioblastomas. Neurosurg Rev 42, 867–876 (2019). https://doi.org/10.1007/s10143-018-01061-5

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Keywords

  • Glioblastoma
  • Texture analysis
  • ADC
  • MGMT