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Metabolic signatures of thymomas: potential biomarkers and treatment targets
James W Miller1, Brandon M Faubert2,3, Thomas P Mathews2
1School of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Objectives:
A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions.
Methods:
From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of >200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions.
Results:
Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P = 0.021, tumour versus benign P = 0.013).
Conclusions:
We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma.
Insights
Metabolomics and 13C-glucose tracing identified unique metabolic biomarkers in thymoma, distinguishing it from benign tissues. These findings highlight altered glucose and lactate metabolism as potential therapeutic targets for thymoma.
Area of Science:
- Oncology
- Metabolomics
- Biochemistry
Background:
- Metabolic reprogramming is a hallmark of cancer, but thymoma metabolism remains poorly understood.
- This study addresses the knowledge gap in thymoma metabolic pathways.
Purpose of the Study:
- To investigate the metabolic landscape of thymoma using metabolomics and isotope tracing.
- To identify potential metabolic biomarkers for thymoma diagnosis and therapeutic targeting.
Main Methods:
- Prospective clinical trial involving 20 patients with suspected thymoma.
- Utilized 13C-glucose isotope tracing and mass spectrometry to analyze >200 metabolites.
- Compared metabolite profiles and 13C enrichment in thymomas, adjacent thymus, and benign lesions.
Main Results:
- Thymomas exhibited distinct metabolite abundances compared to adjacent thymus and benign lesions.
- Differential expression of metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism was observed.
- Increased lactate/3-phosphoglycerate (3PG) labeling ratio in thymoma suggests altered glucose and lactate metabolism.
Conclusions:
- Identified novel metabolic biomarkers, including 13C-labeled metabolites, that differentiate thymoma from benign tissues.
- Altered glucose and lactate metabolism in thymoma present potential therapeutic avenues.
- Further research into these metabolic alterations may lead to new treatment strategies for thymoma.
