Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS

Abstract

Introduction Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. An increasing number of studies have demonstrated that tumor proliferation and metastasis are closely related to complex metabolic reprogramming. However, there are limited data to provide a comprehensive metabolic picture of osteosarcoma. Objectives Our study aims to identify aberrant metabolic pathways and seek potential adjuvant biomarkers for osteosarcoma. Methods Serum samples were collected from 65 osteosarcoma patients and 30 healthy controls. Nontargeted metabolomic profiling was performed by liquid chromatography-mass spectrometry (LC-MS) based on univariate and multivariate statistical analyses. Results The OPLS-DA model analysis identified clear separations among groups. We identified a set of differential metabolites such as higher serum levels of adenosine-5-monophosphate, inosine-5-monophosphate and guanosine monophosphate in primary OS patients compared to healthy controls, and higher serum levels of 5-aminopentanamide, 13(S)-HpOTrE (FA 18:3 + 2O) and methionine sulfoxide in lung metastatic OS patients compared to primary OS patients, revealing aberrant metabolic features during the proliferation and metastasis of osteosarcoma. We found a group of metabolites especially lactic acid and glutamic acid, with AUC values of 0.97 and 0.98, which could serve as potential adjuvant diagnostic biomarkers for primary osteosarcoma, and a panel of 2 metabolites, 5-aminopentanamide and 13(S)-HpOTrE (FA 18:3 + 2O), with an AUC value of 0.92, that had good monitoring ability for lung metastases. Conclusions Our study provides new insight into the aberrant metabolic features of osteosarcoma. The potential biomarkers identified here may have translational significance.

A Key Metabolic Regulator of Bone and Cartilage Health

“…less, taurine has appeared in some of these studies as a possible metabolic marker of bone sarcomas. For example, a serum untargeted metabolomics analysis of 65 patients diagnosed with osteosarcoma revealed higher levels of ascorbic acid, niacinamide, and taurine than in healthy controls [104]. A similar study revealed differences in the synthesis and degradation of ketone bodies and taurine metabolism compared to normal serum [105].…”

Serum Metabolomic Signatures of Hirschsprung’s Disease Based on GC–MS and LC–MS

“…The sample preparation and LC–MS analysis were modified from a previous publication . Thawed serum samples (100 μL) on ice were extracted with 400 μL of cold methanol.…”

“…The sample preparation and LC−MS analysis were modified from a previous publication. 12 Thawed serum samples (100 μL) on ice were extracted with 400 μL of cold methanol. After centrifugation, the supernatant was completely dried by mild nitrogen and the residues were reconstituted in 50 μL of 10% aqueous methanol containing internal standards (1000 ng/mL of phenylalanine-d 5 , 3-chloro-D-phenylalanine, octanoic-d 15 acid, decanoic-d 19 acid, hexadecanoyl-L-carnitine-d 3 , and decanoyl-L-carnitine-d 3 and 100 ng/mL of valine-13 C 5 -15 N, leucine-13 C 6 , and tetradecanoic-d 27 acid) prior to performing UHPLC−HRMS/MS analysis.…”

Evaluation of geranylgeranyl diphosphate synthase inhibition as a novel strategy for the treatment of osteosarcoma and Ewing sarcoma

“…Purines and purine-metabolizing enzymes are essential for tumor cell proliferation and are often upregulated in cancer, making them an attractive therapeutic target (Yin et al, 2018). In one study, serum analysis of 65 OS patient samples and 30 normal controls identified purine metabolism as one of the top aberrantly regulated metabolic pathways in patients with OS (Lv et al, 2020). Another study looking at human OS samples suggest a prognostic value for the expression patterns of the purine-metabolizing enzymes IMPDH2 and HPRT (Chaiyawat et al, 2021).…”