Abstract
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.
Highlights
IntroductionCancer is the disease that causes the most death in children and adolescents in developed countries
Despite being rare, cancer is the disease that causes the most death in children and adolescents in developed countries
The 1H-NMR mean spectra revealed some differences between patients with osteosarcoma and healthy controls, in the regions of δ 0.85–0.89 (m), δ 1.24–1.37 (m), δ 1.55–1.65 (m), δ 1.98– 2.09 (m), and δ 5.29–5.43 (m)
Summary
Cancer is the disease that causes the most death in children and adolescents in developed countries. Osteosarcoma is the commonest primary malignant bone tumor developing during periods of rapid growth [2], with an event-free survival of 60 to 70% in 3 years. 1H-NMR Metabonomics in Osteosarcoma the patients have metastases at diagnosis, whereas ∼40% will develop metastasis during treatment [3]. There were many advances in the field, which contributed to reduced morbidities associated with treatment and management of osteosarcoma over the past few decades [5], no substantial improvement has been achieved in survival rate [6]. Patients with metastatic disease and/or recurrence after treatment continue to have a poor prognosis, with a relapse rate of up to 35% [7, 8]
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