What is the clinical evidence from this study?

Study design: Observational. Population: Patients with osteosarcoma undergoing anthracycline treatment (n=40). Intervention: Anthracycline chemotherapy vs. No anthracycline treatment. Primary outcome: Metabolic profile of amino acids and metabolites assessed by UHPLC-MS/MS and diagnostic performance of metabolites to distinguish ANT treated patients (p=<0.05 for key metabolites).

What does this research mean for the field?

Anthracycline treatment in osteosarcoma patients significantly alters amino acid and metabolite profiles, specifically increasing plasma arginine and six acylcarnitines while decreasing threonine, which can accurately differentiate treated from untreated patients. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The study aimed to explore changes in amino acid metabolism in osteosarcoma patients undergoing anthracycline treatment.

March 1, 2026Open Access

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

Q: What are the key findings of this study?

Anthracycline treatment in osteosarcoma patients increased plasma arginine and six acylcarnitines (AUCs 0.730-0.798) and decreased threonine (AUC 0.682), differentiating treated from untreated with up to 79.8% accuracy.

Q: What does this research mean for the field?

Anthracycline treatment in osteosarcoma patients significantly alters amino acid and metabolite profiles, specifically increasing plasma arginine and six acylcarnitines while decreasing threonine, which can accurately differentiate treated from untreated patients. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

The study aimed to explore changes in amino acid metabolism in osteosarcoma patients undergoing anthracycline treatment.

Key Result

Anthracycline treatment in osteosarcoma patients increased plasma arginine and six acylcarnitines (AUCs 0.730-0.798) and decreased threonine (AUC 0.682), differentiating treated from untreated with up to 79.8% accuracy.

Key Points

The study aimed to explore changes in amino acid metabolism in osteosarcoma patients undergoing anthracycline treatment.
Analyzed plasma amino acids and metabolites in 40 patients with osteosarcoma.
Collected whole blood samples and measured them using ultra-high-performance liquid chromatography-tandem mass spectrometry.
Compared levels of amino acids and metabolites in the ANT group against a control group.
Utilized receiver operating characteristic analysis to identify differential metabolites.
Elevated levels of arginine and reduced levels of threonine were found in patients receiving anthracycline.
Eight metabolites showed significant discriminatory power, with an area under the curve (AUC) exceeding 0.650.
The identified metabolites demonstrated high sensitivity and specificity in identifying patients treated with anthracycline.

Study Design

Type

Observational (n=40)

Multicenter

Structured PICO

Does anthracycline treatment alter the metabolic profile of amino acids and acylcarnitines in patients with osteosarcoma?

Population

40 inpatients with osteosarcoma confirmed by postoperative histology (n=40), treated at a single center. Excluded patients with myocardial infarction, heart failure, myocardial disease, severe kidney disease, recent infection, severe metabolic disease, malnutrition, anemia, recent surgery, liver and hematopoietic disease, autoimmune disease, hyperthyroidism and hypothyroidism, end-stage patients, or receiving amino acid infusion.

Intervention

Anthracycline (ANT) chemotherapy at a dose between 250 mg/m2 and 400 mg/m2, administered for approximately 5 to 12 months.

Comparator

No anthracycline treatment (newly diagnosed osteosarcoma patients who had not yet received chemotherapy).

Outcome

Changes in plasma levels of 48 amino acids and metabolites measured via ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).surrogate

Anthracycline treatment induces significant metabolic reprogramming, characterized by elevated arginine and acylcarnitines, which may serve as early biomarkers for cardiotoxicity preceding LVEF decline.

Main Result

p-value: p=<0.05 for key metabolites

Limitations

Observational case-control design limits causal inference
Small sample size (n=40) limits generalizability
No longitudinal follow-up or LVEF decline observed to correlate metabolic changes with clinical cardiotoxicity
Potential confounders such as diet and medications not controlled
Limited to younger osteosarcoma patients thus may not extrapolate to older populations

Abstract

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.

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