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Integrated semi-targeted metabolomics analysis reveals distinct metabolic dysregulation in pleural effusion caused by
Nanying Che1, Yan Ma2, Huabin Ruan3
1Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, China.
Background:
Tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) are the 2 most frequent causes of exudative pleural effusions (PEs). However, the clinical differentiation is challenging.
Methods:
Metabolic signatures in pleural effusion from 156 patients were profiled. An integrated semi-targeted metabolomics platform was incorporated for high throughput metabolite identification and quantitation. In this platform, orbitrap based mass spectrometry with data dependent MS/MS acquisition was applied in the analysis. In-house database containing ~1000MS/MS spectra were established and "MetaInt" was developed for metabolite alignment.
Results:
Using this strategy, lower levels of amino acids, citric acid cycle intermediates and free fatty acids accompanied with elevated acyl-carnitines and bile acids were observed, demonstrating increased energy expenditure caused by TPE. Kynurenine pathway from tryptophan was significantly enhanced in TPE. The ratio of tryptophan/kynurenine exhibited decent performance in differentiating TPE from MPE with sensitivity of 92.7% and specificity of 86.1%. After two further independent validations, it turns out that the ratio of tryptophan/kynurenine can be applied confidently as a potential biomarker together with adenosine deaminase (ADA) for clinical diagnosis of TPE.
Conclusions:
Conclusively, the integrated in-house platform for high throughput semi-targeted metabolomics analysis reliably identified great potential of tryptophan/kynurenine ratio as a novel diagnostic biomarker to distinguish pleural effusion caused by tuberculosis and malignancy.
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