Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics
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To explore the feasibility of using amide proton transfer-weighted (APTw) MRI metrics as surrogate biomarkers to identify the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in glioblastoma (GBM).
Eighteen newly diagnosed GBM patients, who were previously scanned at 3T and had a confirmed MGMT methylation status, were retrospectively analysed. For each case, a histogram analysis in the tumour mass was performed to evaluate several quantitative APTw MRI metrics. The Mann-Whitney test was used to evaluate the difference in APTw parameters between MGMT methylated and unmethylated GBMs, and the receiver-operator-characteristic analysis was further used to assess diagnostic performance.
Ten GBMs were found to harbour a methylated MGMT promoter, and eight GBMs were unmethylated. The mean, variance, 50th percentile, 90th percentile and Width10-90 APTw values were significantly higher in the MGMT unmethylated GBMs than in the MGMT methylated GBMs, with areas under the receiver-operator-characteristic curves of 0.825, 0.837, 0.850, 0856 and 0.763, respectively, for the discrimination of MGMT promoter methylation status.
APTw signal metrics have the potential to serve as valuable imaging biomarkers for identifying MGMT methylation status in the GBM population.
• APTw-MRI is applied to predict MGMT promoter methylation status in GBMs.
• GBMs with unmethylated MGMT promoter present higher APTw-MRI than methylated GBMs.
• Multiple APTw histogram metrics can identify MGMT methylation status.
• Mean APTw values showed the highest diagnostic accuracy (AUC = 0.825).
KeywordsGlioblastoma O6-methylguanine-DNA methyltransferase Magnetic resonance imaging Amide proton transfer-weighted imaging Methylation
Apparent diffusion coefficient
Amide proton transfer-weighted
Area under the curve
Chemical exchange-dependent saturation transfer
Fluid-attenuated inversion recovery
Magnetic resonance imaging
Receiver operator characteristic curve
The authors thank Ms. Mary McAllister for editorial assistance.
This study was partially supported by grants from National Natural Science Foundation of China (81171322), Guangdong Provincial Natural Science Foundation (2014A030313271, S2012010009114), Guangdong Provincial Science and Technology Project (2014A020212726), Southern Medical University clinical research project (LC2016ZD028), and the National Institutes of Health (R01EB009731, R01CA166171).
Compliance with ethical standards
The scientific guarantor of this publication is Zhibo Wen, MD, PhD.
Conflict of interest
The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
Statistics and biometry
One of the authors (Dr. Fangyao Chen) has significant statistical expertise.
No complex statistical methods were necessary for this paper.
Institutional Review Board approval was obtained.
Written informed consent was waived by the Institutional Review Board.
Study subjects or cohorts overlap
Three study subjects have been previously reported in one of our previous papers, in which we evaluated the diagnostic values of APTw imaging in differentiate PCNSL and malignant gliomas, see Ref. .
• diagnostic or prognostic study
• performed at one institution
- 30.Yu H, Lou H, Zou T et al (2017) Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma. Eur Radiol:DOI. https://doi.org/10.1007/s00330-00017-04867-z
- 34.Choi YS, Ahn SS, Lee SK et al (2017) Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume. Eur Radiol. https://doi.org/10.1007/s00330-00017-04732-00330
- 45.Heo H-Y, Zhang Y, Lee D-H, Hong X, Zhou J (2016) Quantitative assessment of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) imaging with extrapolated semi-solid magnetization transfer reference (EMR) signals: Application to a rat glioma model at 4.7 T. Magn Reson Med 75:137–138CrossRefPubMedGoogle Scholar
- 66.Heo HY, Zhang Y, Jiang S, Lee DH, Zhou J (2016) Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semisolid magnetization transfer reference (EMR) signals: II. Comparison of three EMR models and application to human brain glioma at 3 Tesla. Magn Reson Med 75:1630–1639CrossRefPubMedGoogle Scholar
- 67.Lee DH, Heo HY, Zhang K et al (2017) Quantitative assessment of the effects of water proton concentration and water T1 changes on amide proton transfer (APT) and nuclear overhauser enhancement (NOE) MRI: The origin of the APT imaging signal in brain tumor. Magn Reson Med 77:855–863CrossRefPubMedGoogle Scholar