Exploration of human brain tumour metabolism using pairwise metabolite-metabolite correlation analysis (MMCA) of HR-MAS ¹H NMR spectra

<div><p>Methods</p><p>We quantified 378 HRMAS ¹H NMR spectra of human brain tumours (132 glioblastomas, 101 astrocytomas, 75 meningiomas, 37 oligodendrogliomas and 33 metastases) from the eTumour database and looked for metabolic interactions by metabolite-metabolite correlation analysis (MMCA).</p><p>Results</p><p>All tumour types showed remarkably similar metabolic correlations. Lactate correlated positively with alanine, glutamate with glutamine; creatine + phosphocreatine (tCr) correlated positively with lactate, alanine and choline + phosphocholine + glycerophosphocholine (tCho), and tCho correlated positively with lactate; fatty acids correlated negatively with lactate, glutamate + glutamine (tGlut), tCr and tCho. Oligodendrogliomas had fewer correlations but they still fitted that pattern.</p><p>Conclusions</p><p>Possible explanations include (i) glycolytic tumour cells (the Warburg effect) generating pyruvate which is converted to lactate, alanine, glutamate and then glutamine; (ii) an association between elevated glycolysis and increased choline turnover in membranes; (iii) an increase in the tCr pool to facilitate phosphocreatine-driven glutamate uptake; (iv) lipid signals come from cytosolic lipid droplets in necrotic or pre-necrotic tumour tissue that has lower concentrations of anabolic and catabolic metabolites. Additional metabolite exchanges with host cells may also be involved. If tumours co-opt a standard set of biochemical mechanisms to grow in the brain, then drugs might be developed to disrupt those mechanisms.</p>