Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma

Author(s):Show less -

de Araujo, Rachel Paes ^[1] ; Bertoni, Natalia ^{[2, 3]} ; Seneda, Ana L. ^{[2, 3]} ; Felix, Tainara F. ^{[2, 3]} ; Carvalho, Marcio ^[4] ; Lewis, Keir E. ^{[5, 6]} ; Hasimoto, Erica N. ^[2] ; Beckmann, Manfred ^[1] ; Drigo, Sandra A. ^{[2, 3]} ; Reis, Patricia P. ^{[2, 3]} ; Mur, Luis A. J. ^[1]

Affiliation

^[1] Aberystwyth Univ, IBERS, Aberystwyth SY23 3DA, Ceredigion - Wales

^[2] Sao Paulo State Univ UNESP, Fac Med, Dept Surg & Orthoped, BR-18618687 Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Expt Res Unity UNIPEX, BR-18618687 Botucatu, SP - Brazil

^[4] Sao Paulo State Univ UNESP, Sch Vet Med & Anim Sci, Dept Vet Clin, BR-18618687 Botucatu, SP - Brazil

^[5] Hywel Dda Univ Hlth Board, Prince Philip Hosp, Clin Res Ctr, Llanelli SA14 8QF - Wales

^[6] Swansea Univ, Sch Med, Singleton Pk, Swansea SA2 8PP, W Glam - Wales

• Document type: Journal article
• Source: METABOLITES; v. 9, n. 3 MAR 7 2019.
• Web of Science Citations: 2

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 gamma-aminobutyric acid (GABA). Our results show the value of FIE-HRMS as a high throughput screening method that could be exploited in clinical contexts. (AU)

• FAPESP's process: 16/50429-1 - Luis Alejandro Jose Mur | Aberystwyth University - País de Gales
• Grantee: Patricia Pintor dos Reis
• Support Opportunities: Research Grants - Visiting Researcher Grant - International