Insights in Osteosarcoma by Proton Nuclear Magnetic Resonance Serum Metabonomics

Pediatric osteosarcoma outcomes have improved over the last decades, however, patients that do not achieve a full resection of the tumor, even after aggressive chemotherapy, have the worst prognosis. At genetic level, osteosarcoma presents many alterations but there is a scarce information on alterations at metabolomic levels. Therefore, an untargeted NMR-metabonomic approach was used to reveal blood serum alterations, when samples taken from twenty-one (21) patients with osteosarcoma aged from 12-20 (18, 86%) to 43 (3, 14%) 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 points to protons of the fatty acyls (-CH3 and -CH2-) from a very low- and low-density lipoproteins (VLDL and LDL) 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 NMR could be successfully applied for osteosarcoma diagnostic and prognostic purposes, which could ameliorate the clinical efficacy of therapy.