Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma

Rachel Paes De Araujo, Natália Bertoni, Ana L. Seneda, Tainara Felix, Márcio Carvalho, Keir E. Lewis, Érica N. Hasimoto, Manfred Beckmann, Sandra A. Drigo, Patricia P. Reis, Luis Mur

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Abstract

Metabolomics based on untargeted flow infusion electrospray ionization high-resolution mass spectrometry (FIE-HRMS) can provide a snap-shot of metabolism in living cells. Lung Squamous Cell Carcinoma (SCC) is one of the predominant subtypes of Non-Small Cell Lung Cancers (NSCLCs), which usually shows a poor prognosis. We analysed lung SCC samples and matched histologically normal lung tissues from eight patients. Metabolites were profiled by FIE-HRMS and assessed using t-test and principal component analysis (PCA). Differentially accumulating metabolites were mapped to pathways using the mummichog algorithm in R, and biologically meaningful patterns were indicated by Metabolite Set Enrichment Analysis (MSEA). We identified metabolic rewiring networks, including the suppression of the oxidative pentose pathway and found that the normal tricarboxylic acid (TCA) cycle were decoupled from increases in glycolysis and glutamine reductive carboxylation. Well-established associated effects on nucleotide, amino acid and thiol metabolism were also seen. Novel aspects in SCC tissue were increased in Vitamin B complex cofactors, serotonin and a reduction of γ-aminobutyric acid (GABA). Our results show the value of FIE-HRMS as a high throughput screening method that could be exploited in clinical contexts
Original languageEnglish
Article number47
JournalMetabolites
Volume9
Issue number3
DOIs
Publication statusPublished - 07 Mar 2019

Keywords

  • lung squamous cell carcinoma
  • flow infusion electrospray ionization high resolution mass spectrometry
  • untargeted metabolites
  • pathways
  • Untargeted metabolites
  • Pathways
  • Flow infusion electrospray ionization high resolution mass spectrometry
  • Lung squamous cell carcinoma

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