Targeting the metabolic fingerprint of amino acids to identify novel metabolic characteristics in osteosarcoma patients undergoing anthracycline treatment

Anthracycline (ANT) is a potent chemotherapeutic drug used in the treatment of solid tumors. However, its clinical use is limited by the occurrence of severe cardiotoxicity, which can lead to cardiac dilation and heart failure. Unfortunately, the exact mechanism behind this cardiotoxicity is not well understood. To address this gap in knowledge, our study aimed to investigate the changes in amino acid metabolism before and after receiving ANT treatment. We conducted a comprehensive analysis of the metabolic profile, measuring plasma levels of amino acids and other metabolites. 40 Patients with osteosarcoma who were consecutively admitted to Peking University People’s Hospital for ANT treatment were included in this study. Whole blood samples were collected and analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to quantify the levels of 48 amino acids and metabolites. Our findings indicate that levels of arginine (Arg) were found to be elevated, while threonine (Thr) levels were reduced in the anthracycline (ANT) group. A comparison of metabolites with increased concentrations, including C12:1, C10:1, C12, C10, C5DC, and C8, was conducted against a control group. Subsequently, we assessed eight differential metabolites within the ANT group utilizing receiver operating characteristic (ROC) analysis. The eight identified amino acids and metabolites demonstrated significant discriminatory power in differentiating patients receiving anthracycline treatment from those who were not. An area under the curve (AUC) exceeding 0.650 suggests that these biomarkers possess high accuracy in identifying patients with ANT. Furthermore, the optimal sensitivity and specificity values reinforce their efficacy in accurately classifying individuals. The findings indicate that these alterations in amino acids and metabolites may serve as potential metabolic characteristics for predicting the development or presence of conditions before and after receiving ANT treatment. Through the utilization of targeted metabolic profiling surveys, we have identified several alterations in amino acids and metabolites before and after the administration of ANT treatment.