Identification of metabolites in plasma for predicting survival in glioblastoma

Mol Carcinog. 2018 Aug;57(8):1078-1084. doi: 10.1002/mc.22815. Epub 2018 Apr 16.

Abstract

Circulating metabolomics profiling holds prognostic potential. However, such efforts have not been extensively carried out in glioblastoma. In this study, two-step (training and testing) metabolomics profiling was conducted from the plasma samples of 159 glioblastoma patients. Metabolomics profiling was tested for correlation with 2-year overall and disease-free survivals. Arginine, methionine, and kynurenate levels were significantly associated with 2-year overall survival in both the training and testing sets. In the combined sets, elevated levels of arginine and methionine were associated with a 34% and 37% increased probability whereas kynurenate was associated with a 55% decreased probability of 2-year overall survival. These three metabolites were also significantly associated with 2-year disease-free survival. Risk scores were generated using the linear combination of levels of these significant metabolites. Glioblastoma patients with a high-risk score exhibited a 2.41-fold decreased probability of 2-year overall survival (hazard ratio (HR) = 2.41; 95% Confidence Interval (CI) = 1.20-4.93) and a 3.17-fold decreased probability of 2-year disease free survival (HR = 3.17, 95%CI = 1.42-7.54) relative to those with a low-risk score. In conclusion, we identified a unique plasma metabolite profile that is predictive of glioblastoma prognosis.

Keywords: glioblastoma; metabolomics; survival.

MeSH terms

  • Adult
  • Arginine / blood
  • Arginine / metabolism
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / blood*
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism
  • Disease-Free Survival
  • Female
  • Glioblastoma / blood*
  • Glioblastoma / diagnosis
  • Glioblastoma / metabolism
  • Humans
  • Kynurenic Acid / blood
  • Kynurenic Acid / metabolism
  • Male
  • Metabolome
  • Metabolomics
  • Methionine / blood
  • Methionine / metabolism
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • Arginine
  • Methionine
  • Kynurenic Acid