TY - JOUR
T1 - Insights in Osteosarcoma by Proton Nuclear Magnetic Resonance Serum Metabonomics
AU - Quintero Escobar, Melissa
AU - Costa, Tássia Brena Barroso Carneiro
AU - Martins, Lucas G.
AU - Costa, Silvia S.
AU - vanHelvoort Lengert, André
AU - Boldrini, Erica
AU - Morini da Silva, Sandra Regina
AU - Lopes, Luiz Fernando
AU - Vidal, Daniel Onofre
AU - Krepischi, Ana C.V.
AU - Maschietto, Mariana
AU - Tasic, Ljubica
N1 - Funding Information:
This research was financially supported by the São Paulo Research Foundation (FAPESP 2014/10250-7; 2015/06281-7; 2018/06510-4; 2018/21047-9, São Paulo, Brazil), the National Council for Scientific and Technological Development (CNPq, Brasilia, Brazil), National Institute of Science and
Publisher Copyright:
© Copyright © 2020 Quintero Escobar, Costa, Martins, Costa, vanHelvoort Lengert, Boldrini, Morini da Silva, Lopes, Vidal, Krepischi, Maschietto and Tasic.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/16
Y1 - 2020/10/16
N2 - Pediatric osteosarcoma outcomes have improved over the last decades; however, patients who do not achieve a full resection of the tumor, even after aggressive chemotherapy, have the worst prognosis. At a genetic level, osteosarcoma presents many alterations, but there is scarce information on alterations at metabolomic levels. Therefore, an untargeted nuclear magnetic resonance metabonomic approach was used to reveal blood serum alterations, when samples were taken from 21 patients with osteosarcoma aged from 12–20 (18, 86%) to 43 (3, 14%) years before any anticancer therapy were collected. The results showed that metabolites differed greatly between osteosarcoma and healthy control serum samples, especially in lipids, aromatic amino acids (phenylalanine and tyrosine), and histidine concentrations. Besides, most of the loading plots point to protons of the fatty acyls (-CH3 and -CH2-) from very-low- and low-density lipoproteins and cholesterol, as crucial metabolites for discrimination of the patients with osteosarcoma from the healthy samples. The relevance of blood lipids in osteosarcoma was highlighted when analyzed together with the somatic mutations disclosed in tumor samples from the same cohort of patients, where six genes linked to the cholesterol metabolism were found being altered too. The high consistency of the discrimination between osteosarcoma and healthy control blood serum suggests that nuclear magnetic resonance could be successfully applied for osteosarcoma diagnostic and prognostic purposes, which could ameliorate the clinical efficacy of therapy.
AB - Pediatric osteosarcoma outcomes have improved over the last decades; however, patients who do not achieve a full resection of the tumor, even after aggressive chemotherapy, have the worst prognosis. At a genetic level, osteosarcoma presents many alterations, but there is scarce information on alterations at metabolomic levels. Therefore, an untargeted nuclear magnetic resonance metabonomic approach was used to reveal blood serum alterations, when samples were taken from 21 patients with osteosarcoma aged from 12–20 (18, 86%) to 43 (3, 14%) years before any anticancer therapy were collected. The results showed that metabolites differed greatly between osteosarcoma and healthy control serum samples, especially in lipids, aromatic amino acids (phenylalanine and tyrosine), and histidine concentrations. Besides, most of the loading plots point to protons of the fatty acyls (-CH3 and -CH2-) from very-low- and low-density lipoproteins and cholesterol, as crucial metabolites for discrimination of the patients with osteosarcoma from the healthy samples. The relevance of blood lipids in osteosarcoma was highlighted when analyzed together with the somatic mutations disclosed in tumor samples from the same cohort of patients, where six genes linked to the cholesterol metabolism were found being altered too. The high consistency of the discrimination between osteosarcoma and healthy control blood serum suggests that nuclear magnetic resonance could be successfully applied for osteosarcoma diagnostic and prognostic purposes, which could ameliorate the clinical efficacy of therapy.
KW - bone cancer
KW - lipid alterations
KW - metabonomics
KW - NMR
KW - osteosarcoma
KW - pediatric cancers
UR - https://hdl.handle.net/20.500.12724/11896
UR - http://www.scopus.com/inward/record.url?scp=85094808948&partnerID=8YFLogxK
U2 - 10.3389/fonc.2020.506959
DO - 10.3389/fonc.2020.506959
M3 - Artículo (Contribución a Revista)
AN - SCOPUS:85094808948
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 506959
ER -