Bioanalysis of a panel of neurotransmitters and their metabolites in plasma samples obtained from pediatric patients with neuroblastoma and Wilms' tumor

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Feb 1:1074-1075:99-110. doi: 10.1016/j.jchromb.2017.12.031. Epub 2017 Dec 28.

Abstract

This paper details the quantitative analysis of neurotransmitters, including dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT), along with their respective precursors and metabolites in children with solid tumors: Wilms' tumor (WT) and neuroblastoma (NB). A panel of neurotransmitters was determined with the use of dispersive liquid-liquid microextraction (DLLME) technique combined with liquid-chromatography mass spectrometry (LC-MS/MS) in plasma samples obtained from a group of pediatric subjects with solid tumors and a control group of healthy children. Next, statistical univariate analysis (t-test) and multivariate analysis (Principal Component Analysis) were performed using chromatographic data. The levels of tyrosine (Tyr) and tryptophan (Trp) (the precursors of analyzed neurotransmitters) as well as 3,4-dihydroxyphenylacetic acid (DOPAC) (a product of metabolism of DA) were significantly higher in the plasma samples obtained from pediatric patients with WT than in the samples taken from the control group. Moreover, statistically significant differences were observed between the levels of 5-HT and homovanillic acid (HVA) in the plasma samples from pediatric patients with solid tumors and the control group. However, elevated levels of these analytes did not facilitate a clear distinction between pediatric patients with WT and those with NB. Nonetheless, the application of advanced statistical tools allowed the healthy controls to be differentiated from the pediatric oncological patients. The identification and quantification of a panel of neurotransmitters as potential prognostic factors in selected childhood malignancies may provide clinically relevant information about ongoing metabolic alterations, and it could potentially serve as an adjunctive strategy in the effective diagnosis and treatment of solid tumors in children.

Keywords: DLLME; Neuroblastoma; Neurotransmitter; Pediatric patients; Wilms' tumor.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Humans
  • Infant
  • Infant, Newborn
  • Limit of Detection
  • Linear Models
  • Neuroblastoma / blood
  • Neuroblastoma / metabolism*
  • Neurotransmitter Agents / blood*
  • Neurotransmitter Agents / chemistry
  • Neurotransmitter Agents / metabolism
  • Principal Component Analysis
  • Reproducibility of Results
  • Tandem Mass Spectrometry
  • Wilms Tumor / blood
  • Wilms Tumor / metabolism*

Substances

  • Neurotransmitter Agents