Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS
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ORIGINAL ARTICLE
Comprehensive metabolomic profiling of osteosarcoma based on UHPLC‑HRMS Dongming Lv1,2 · Yutong Zou1,2 · Ziliang Zeng1,2 · Hao Yao1,2 · Shirong Ding4 · Yiying Bian1,2 · Lili Wen3 · Xianbiao Xie1,2 Received: 3 April 2020 / Accepted: 9 November 2020 © The Author(s) 2020
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. Keywords Metabolomics · Osteosarcoma · LC-MS · Biomarker
1 Introduction Electronic supplementary material The online version of this article (doi:https://doi.org/10.1007/s11306-020-01745-4) contains supplementary material, which is available to authorized users. * Lili Wen [email protected] * Xianbiao Xie [email protected] 1
Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, People’s Republic of China
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou 510080, People’s Republic of China
2
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, mainly occurring between the ages of 10 and 25 years (Isakoff et al. 2015). With the 3
Department of Anesthesiology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Gu
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