TY - JOUR
T1 - A Metabonomic View on Wilms Tumor by High-Resolution Magic-Angle Spinning Nuclear Magnetic Resonance Spectroscopy
AU - Tasic, Ljubica
AU - Avramović, Nataša
AU - Quintero, Melissa
AU - Stanisic, Danijela
AU - Martins, Lucas G.
AU - da Costa, Tassia Brena Barroso Carneiro
AU - Jadranin, Milka
AU - de Souza Accioly, Maria Theresa
AU - Faria, Paulo
AU - de Camargo, Beatriz
AU - de Sá Pereira, Bruna M.
AU - Maschietto, Mariana
N1 - Funding Information:
Acknowledgments: On this occasion, we would like to thank the funding agencies, especially Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grants #2018/24069-3, #2018/06510-4, and #2014/10250-7. NMR experiments were carried out in the Institute of Chemistry, NMR Spectroscopy Open Facility Laboratory, State University of Campinas. We kindly acknowledge the National Cancer Institute (INCA) and National Bank of Tumor staff involved in tissue collection and storage. Last but not least, we are very grateful to the children, and their parents and caretakers for taking part in this important study.
Funding Information:
Funding: This research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grants numbers #2018/24069-3, #2018/06510-4, and #2014/10250-7. M.J. was funded by the International Cooperation Branch, Organisation for the Prohibition of Chemical Weapons (OPCW), Hague, The Netherlands, grant number L/ICA/ICB/221146/19. We kindly acknowledge INCTBio (CNPq 465389/2014-7 and FAPESP #2014/50867-3) for financial support.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1/10
Y1 - 2022/1/10
N2 - 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 HRMAS T2-edited1H-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.
AB - 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 HRMAS T2-edited1H-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.
KW - Metabolic pathways
KW - NMR-metabonomics
KW - Wilms tumor (WT)
UR - http://www.scopus.com/inward/record.url?scp=85122657154&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/c20975b7-3cba-3a2a-95a0-03aa7884ad05/
U2 - 10.3390/diagnostics12010157
DO - 10.3390/diagnostics12010157
M3 - Artículo (Contribución a Revista)
AN - SCOPUS:85122657154
SN - 2075-4418
VL - 12
SP - 1
EP - 10
JO - Diagnostics
JF - Diagnostics
IS - 1
M1 - 157
ER -
