Plasma amino acids indicate glioblastoma with ATRX loss

Amino Acids. 2021 Jan;53(1):119-132. doi: 10.1007/s00726-020-02931-3. Epub 2021 Jan 4.


Glioblastoma (GB) is the most common primary brain tumour in adults. The lack of molecular biomarker, non-specific symptoms and fast growth rate often result in a significant delay in diagnosis. Despite multimodal treatment, the prognosis remains poor. Here, we verified the hypothesis that amino acids (AA) regulating the critical metabolic pathways necessary for maintenance, growth, reproduction, and immunity of an organism, may constitute a favourable target in GB biomarker research. We measured the plasma amino acids levels in 18 GB patients and 15 controls and performed the quantitative and qualitative metabolomic analysis of free AA applying high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). We present both the raw data and the results of our statistical analysis. The majority of AA were lowered in the study group in comparison to the control group. Five of these (arginine, glutamic acid, glutamine, glycine, and histidine) differed significantly (all p < 10-5 and AUC > 0.9). Plasma levels of leucine and phenylalanine decreased in the case of GB with lost alpha-thalassemia/mental retardation X-linked (ATRX) expression on immunohistochemistry (p = 0.003 and 0.045, respectively). We demonstrated for the first time that certain plasma-free AA levels of GB patients were significantly different from those in healthy volunteers. Target profiling of plasma-free AA, identified utilizing LC-QTOF-MS, may present prognostic value by indicating GB patients with lost ATRX expression. The on-going quest for glioma biomarkers still aims to determine the detailed metabolic profile and evaluate its impact on therapy and prognosis.

Keywords: Amino acid; Biomarker; Glioblastoma; Immunohistochemistry; Plasma.

MeSH terms

  • Aged
  • Amino Acids / blood*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / blood
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism*
  • Female
  • Glioblastoma / blood
  • Glioblastoma / diagnosis
  • Glioblastoma / metabolism*
  • Humans
  • Male
  • Metabolomics
  • Middle Aged
  • Prognosis
  • X-linked Nuclear Protein / metabolism*


  • Amino Acids
  • Biomarkers, Tumor
  • ATRX protein, human
  • X-linked Nuclear Protein