Discriminating MGMT promoter methylation status in patients with glioblastoma employing amide proton transfer-weighted MRI metrics

Eur Radiol. 2018 May;28(5):2115-2123. doi: 10.1007/s00330-017-5182-4. Epub 2017 Dec 12.

Abstract

Objectives: 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).

Methods: 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.

Results: 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.

Conclusions: APTw signal metrics have the potential to serve as valuable imaging biomarkers for identifying MGMT methylation status in the GBM population.

Key points: • 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).

Keywords: Amide proton transfer-weighted imaging; Glioblastoma; Magnetic resonance imaging; Methylation; O6-methylguanine-DNA methyltransferase.

MeSH terms

  • Adult
  • Aged
  • Amides / chemistry*
  • Biomarkers / metabolism
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • Female
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic
  • Protons
  • ROC Curve
  • Retrospective Studies
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Young Adult

Substances

  • Amides
  • Biomarkers
  • Protons
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes