Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS.

Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS.
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DOI:
10.1007/s11306-020-01745-4
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发表时间:
2020-11-18
期刊:
Metabolomics : Official journal of the Metabolomic Society
影响因子:
--
通讯作者:
Xie X
Xie X
中科院分区:
其他
文献类型:
--
作者:
Lv D;Zou Y;Zeng Z;Yao H;Ding S;Bian Y;Wen L;Xie X

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骨肉瘤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,有有限的数据,以提供一个全面的骨肉瘤代谢图片。我们的研究旨在确定骨肉瘤的异常代谢途径,并寻求潜在的辅助生物标志物。收集65例骨肉瘤患者和30例健康对照者的血清样本。基于单变量和多变量统计分析,通过液相色谱-质谱法(LC-MS)进行非靶向代谢组学分析。OPLS-DA模型分析确定了组间的明显分离。我们鉴定了一组差异代谢物,例如与健康对照相比,原发性OS患者中腺苷-5-单磷酸、肌苷-5-单磷酸和鸟苷单磷酸的血清水平更高,并且与原发性OS患者相比,肺转移性OS患者中5-氨基戊酰胺、13(S)-HpOTrE(FA 18:3 + 2 O)和甲硫氨酸亚砜的血清水平更高,揭示了骨肉瘤增殖和转移期间的异常代谢特征。我们发现了一组代谢物,尤其是乳酸和谷氨酸,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 + 2 O),AUC值为0.92,对肺转移具有良好的监测能力。我们的研究为骨肉瘤的异常代谢特征提供了新的见解。这里鉴定的潜在生物标志物可能具有翻译意义。本文的在线版本(doi:10.1007/s11306-020-01745-4)包含补充材料,可供授权用户使用。
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. Our study aims to identify aberrant metabolic pathways and seek potential adjuvant biomarkers for osteosarcoma. 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. 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. Our study provides new insight into the aberrant metabolic features of osteosarcoma. The potential biomarkers identified here may have translational significance. The online version of this article (doi:10.1007/s11306-020-01745-4) contains supplementary material, which is available to authorized users.
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