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.

中文翻译：

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基于 UHPLC-HRMS 的骨肉瘤综合代谢组学分析

介绍

骨肉瘤（OS）是儿童和青少年最常见的原发性恶性骨肿瘤。越来越多的研究表明，肿瘤的增殖和转移与复杂的代谢重编程密切相关。然而，提供骨肉瘤综合代谢情况的数据有限。

目标

我们的研究旨在识别异常代谢途径并寻找潜在的骨肉瘤辅助生物标志物。

方法

从 65 名骨肉瘤患者和 30 名健康对照者收集血清样品。通过基于单变量和多变量统计分析的液相色谱-质谱法 (LC-MS) 进行非靶向代谢组学分析。

结果

OPLS-DA 模型分析确定了组之间的明显分离。我们确定了一组差异代谢物，例如与健康对照相比，原发性 OS 患者的 5-单磷酸腺苷、5-单磷酸肌苷和单磷酸鸟苷的血清水平更高，以及 5-氨基戊酰胺、13(S)-与原发性 OS 患者相比，肺转移性 OS 患者的 HpOTrE (FA 18:3 + 2O) 和甲硫氨酸亚砜，揭示了骨肉瘤增殖和转移过程中的异常代谢特征。我们发现了一组代谢物，尤其是乳酸和谷氨酸，其 AUC 值为 0.97 和 0.98，可作为原发性骨肉瘤的潜在辅助诊断生物标志物，以及一组 2 种代谢物，5-氨基戊酰胺和 13(S)-HpOTrE (FA 18:3 + 2O)，AUC 值为 0.92，

结论

我们的研究为骨肉瘤的异常代谢特征提供了新的见解。这里确定的潜在生物标志物可能具有转化意义。