A Metabonomic View on Wilms Tumor by High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance Spectroscopy

Author(s):Show less -

Tasic, Ljubica ^[1] ; Avramovic, Natasa ^[2] ; Quintero, Melissa ^[1] ; Stanisic, Danijela ^[1] ; Martins, Lucas G. ^[1] ; da Costa, Tassia Brena Barroso Carneiro ^{[1, 3]} ; Jadranin, Milka ; de Souza Accioly, Maria Theresa ^[4] ; Faria, Paulo ^[5] ; de Camargo, Beatriz ^[6] ; de Sa Pereira, Bruna M. ^[6] ; Maschietto, Mariana ^[7]

Affiliation

^[1] Univ Campinas UNICAMP, Inst Chem, Lab Biol Chem, BR-13083970 Campinas, SP - Brazil

^[2] Univ Belgrade, Inst Med Chem, Fac Med, Visegradska 26, Belgrade 11000 - Serbia

^[3] Univ Belgrade, Inst Chem Technol & Met, Dept Chem, Belgrade 11000 - Serbia

^[4] Natl Bank Tumors Natl Canc Inst BNT INCA, BR-20231091 Rio De Janeiro - Brazil

^[5] Fed Univ Rio Janeiro UFRJ, Dept Pathol, BR-21941901 Rio De Janeiro - Brazil

^[6] Natl Canc Inst INCA, Clin Res Dept, BR-20231091 Rio De Janeiro - Brazil

^[7] Natl Ctr Res Energy & Mat CNPEM, Natl Lab Biosci LNBio, Campinas - Brazil

• Document type: Journal article
• Source: DIAGNOSTICS; v. 12, n. 1 JAN 2022.
• Web of Science Citations: 0

Abstract

Pediatric cancer NMR-metabonomics might be a powerful tool to discover modified biochemical pathways in tumor development, improve cancer diagnosis, and, consequently, treatment. Wilms tumor (WT) is the most common kidney tumor in young children whose genetic and epigenetic abnormalities lead to cell metabolism alterations, but, so far, investigation of metabolic pathways in WT is scarce. We aimed to explore the high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) metabonomics of WT and normal kidney (NK) samples. For this study, 14 WT and 7 NK tissue samples were obtained from the same patients and analyzed. One-dimensional and two-dimensional HR-MAS NMR spectra were processed, and the one-dimensional NMR data were analyzed using chemometrics. Chemometrics enabled us to elucidate the most significant differences between the tumor and normal tissues and to discover intrinsic metabolite alterations in WT. The metabolic differences in WT tissues were revealed by a validated PLS-DA applied on HR-MAS T-2-edited H-1-NMR and were assigned to 16 metabolites, such as lipids, glucose, and branched-chain amino acids (BCAAs), among others. The WT compared to NK samples showed 13 metabolites with increased concentrations and 3 metabolites with decreased concentrations. The relative BCAA concentrations were decreased in the WT while lipids, lactate, and glutamine/glutamate showed increased levels. Sixteen tissue metabolites distinguish the analyzed WT samples and point to altered glycolysis, glutaminolysis, TCA cycle, and lipid and BCAA metabolism in WT. Significant variation in the concentrations of metabolites, such as glutamine/glutamate, lipids, lactate, and BCAAs, was observed in WT and opened up a perspective for their further study and clinical validation. (AU)

• FAPESP's process: 14/10250-7 - Characterization of the epigenetic regulation in human solid paediatric tumours
• Grantee: Mariana Camargo Maschietto
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health
• Grantee: Fernando Barbosa Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/06510-4 - Application of Nuclear Magnetic Resonance (NMR) in metabolomics and metabonomics of human diseases
• Grantee: Ljubica Tasic
• Support Opportunities: Regular Research Grants