Serum and Urinary Metabonomic Study of Human Osteosarcoma

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor found in children. Currently, researchers have focused on protein and gene levels, while the associated metabolic variations have been poorly understood. In this study, we used a gas chromatography mass spectrometry approach and profiled small-molecule metabolites in serum and urine of 24 OS patients, 19 benign bone tumor patients, and 32 healthy controls, to determine whether there are significant alterations associated with carcinogenesis. The metabonomic results demonstrate clear intergroup separations between healthy control subjects and bone tumor patients in the orthogonal partial least-squares-discriminant analysis (OPLS-DA) models. Differential metabolites identified from the metabonomic analysis suggest a disrupted energy metabolism in OS patients, as characterized by significantly down-regulated TCA cycle and glycolysis, down-regulated lipid metabolism, dysregulated sugar levels, and up-regulated amino acid metabolism. Additionally, an increased activity of glutathione metabolism, and increased polyamine metabolism also contributed to a characteristic metabolic signature of OS patients.

NMR-based Metabolomic Analysis of Human Bladder Cancer

“…28 The levels of intermediates of glucose metabolism (citrate and lactate) were markedly lowered in serum samples from BC patients compared with those from healthy subjects, which might account for the accumulation of glucose observed in this study. The reduced levels of lactate was also observed in some types of cancers, such as osteosarcoma, 14 head and neck cancer. 29 However, these observations are strikingly different from the well known "Warburg effect" where, commonly, lactate levels are high in tumor tissues.…”

“…To guard against model overfitting, we validated the supervised models with a 200 times permutation test. 14 Statistical analysis was performed using the SPSS software (Ver. 11.0, SPSS Inc., USA).…”

Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma

“…Zhang et al (2010) used gas chromatography mass spectrometry approach and profiled small-molecule metabolites to observe metabolic variations in urine and serum of patients with osteosarcoma; the author notes a disrupted energy metabolism, down-regulated lipid metabolism, dysregulated sugar levels, up-regulated amino acid metabolism, increase of glutathione metabolism and polyamine metabolism (Zhang et al, 2010). …”

Metabonomics

“…Applications of GC-TOFMS-based metabonomic analyses were reported for biomarker discovery and elucidation of pathogenesis of various diseases such as diabetes [16,99], hepatocellular carcinoma [100], kidney cancer [31], bladder cancer [54], colorectal cancer [101], ovarian cancer [62], osteosarcoma [102], acute coronary syndrome [103], and Crohn's disease [104].…”