Impact of post-surgical freezing delay on brain tumor metabolomics

Metabolomics. 2019 May 13;15(5):78. doi: 10.1007/s11306-019-1541-2.

Abstract

Introduction: Translational cancer research has seen an increasing interest in metabolomic profiling to decipher tumor phenotypes. However, the impact of post-surgical freezing delays on mass spectrometric metabolomic measurements of the cancer tissue remains elusive.

Objectives: To evaluate the impact of post-surgical freezing delays on cancer tissue metabolomics and to investigate changes per metabolite and per metabolic pathway.

Methods: We performed untargeted metabolomics on three cortically located and bulk-resected glioblastoma tissues that were sequentially frozen as duplicates at up to six different time delays (0-180 min, 34 samples).

Results: Statistical modelling revealed that 10% of the metabolome (59 of 597 metabolites) changed significantly after a 3 h delay. While carbohydrates and energy metabolites decreased, peptides and lipids increased. After a 2 h delay, these metabolites had changed by as much as 50-100%. We present the first list of metabolites in glioblastoma tissues that are sensitive to post-surgical freezing delays and offer the opportunity to define individualized fold change thresholds for future comparative metabolomic studies.

Conclusion: More researchers should take these pre-analytical factors into consideration when analyzing metabolomic data. We present a strategy for how to work with metabolites that are sensitive to freezing delays.

Keywords: MetaboDiff; Metabolome; Quenching; Snap-frozen.

MeSH terms

  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / surgery*
  • Carbohydrates
  • Freezing*
  • Glioblastoma / metabolism
  • Glioblastoma / surgery
  • Humans
  • Metabolic Networks and Pathways
  • Metabolome*
  • Metabolomics / methods*
  • Peptides
  • Time Factors

Substances

  • Carbohydrates
  • Peptides