Metabolomic pattern of childhood neuroblastoma obtained by 1H‐high‐resolution magic angle spinning (HRMAS) NMR spectroscopy

Abstract

The aim of this preliminary study is to characterize by ¹H high-resolution magic angle spinning NMR spectroscopy (HRMAS) the metabolic content of intact biopsy samples obtained from 12 patients suffering from neuroblastoma (NB). The biochemical NB profile was first compared to normal adrenal medulla. In a second step, the relationship between the tumor metabolic profile and the patients' clinical data was investigated. A higher level of creatine, glutamine/glutamate, acetate and glycine characterized NB biopsies while healthy adrenal medulla tissue contained adrenaline and a larger amount of ascorbic acid. Adrenaline, which was undetectable in NB spectra, represented the metabolic signature of normal adrenal medulla. NB from patients younger than 12 months contained a higher level of acetate and lysine. Conversely, higher amounts of glutathione, glutamate, myo-inositol, glycine, serine and ascorbic acid were detected in NB samples belonging to younger children. Glutamine/glutamate, aspartate, creatine, glycine were characteristic of stage I-II NB. Acetate and creatine were characteristic of stage IV NB. Finally, a relatively higher amount of aspartate, succinate, and glutathione was detected in patients alive without active disease after a mean follow-up of 7 years whereas a higher concentration of acetate and taurine was characteristic of patients with worse prognosis. Our preliminary results suggest the existence of a complex metabolic reality in NB, probably representative of tumor behavior. However, the real impact of these promising results should be assessed by long-term prospective studies on a larger cohort of patients.