Cho/Cr ratio at MR spectroscopy as a biomarker for cellular proliferation activity and prognosis in glioma: correlation with the expression of minichromosome maintenance protein 2

Acta Radiol. 2019 Jan;60(1):106-112. doi: 10.1177/0284185118770899. Epub 2018 Apr 17.

Abstract

Background: Magnetic resonance (MR) spectroscopy (1H-MRS) has been demonstrated to be useful in grading glioma, but the utility in assessing cellular proliferation activity and prognosis correlated with the expression of minichromosome maintenance protein 2 (MCM2) has not been reported.

Purpose: To explore the correlation between proton MR spectroscopy parameters (including choline [Cho]/creatine [Cr], N-acetyl aspartate [NAA]/Cr, and Cho/NAA ratios) and the expression of MCM2 and to further evaluate whether 1H-MRS can predict cell proliferative activity and provide prognostic information in high-grade gliomas (HGGs).

Material and methods: Forty-three patients with histopathologically confirmed gliomas were involved in this study. All patients underwent 1H-MRS examination before surgery. Proliferative activity of gliomas was evaluated by MCM2 labeling index (LI). Pearson correlation analysis and empiric receiver operating characteristic (ROC) curves were performed. The Kaplan-Meier method and Cox regression were used for survival analysis.

Results: Significant correlation was observed between the Cho/Cr ratio and MCM2 LI ( r = 0.522, P < 0.01); however, there was no correlation between MCM2 LI and the Cho/NAA or NAA/Cr ratios ( r = 0.295, P = 0.55 and r = -0.042, P = 0.788, respectively). According to ROC analysis, MCM2 LI of 50% and Cho/Cr ratio of 2.68 represented the optimized cut-off values, respectively, to distinguish longer or shorter survival than 15 months in HGGs patients. Multivariate analysis revealed that both the Cho/Cr ratio and MCM2 expression were independent prognostic markers.

Conclusion: Cho/Cr ratio has a potential in predicting the expression of MCM2 and can evaluate cell proliferative activity noninvasively. Both the Cho/Cr ratio and MCM2 expression are independent prognostic markers in patients with HGGs.

Keywords: 1H-MRS; Glioma; MCM2; cellular proliferation; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aspartic Acid / analogs & derivatives
  • Biomarkers / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Proliferation / physiology*
  • Child
  • Choline / metabolism*
  • Creatine / metabolism*
  • Female
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Minichromosome Maintenance Complex Component 2 / genetics
  • Minichromosome Maintenance Complex Component 2 / metabolism*
  • Neoplasm Grading
  • Survival Analysis
  • Young Adult

Substances

  • Biomarkers
  • Aspartic Acid
  • N-acetylaspartate
  • MCM2 protein, human
  • Minichromosome Maintenance Complex Component 2
  • Creatine
  • Choline