Identification of the molecular mechanism and diagnostic biomarkers in the thoracic ossification of the ligamentum flavum using metabolomics and transcriptomics.

BACKGROUND: To establish a metabolite fingerprint of ossification of the thoracic ligamentum flavum (OTLF) patients using liquid chromatography-mass spectrometry (LC-MS) in combination with transcriptomic data and explore the potential molecular mechanism of pathogenesis. RESULTS: The study cohort was composed of 25 patients with OTLF and 23 healthy volunteers as a control group. Thirty-seven metabolites were identified out by UPLC-MS including uric acid and hypoxanthine. Nine metabolites, including uric acid and hypoxanthine, were found with a Variable Importance in Projection (VIP) score over 1 (p < 0.05). Pathway enrichment indicated that purine metabolism pathways and the other four metabolism pathways were enriched. Transcriptomic data revealed that purine metabolism have a substantial change in gene expression of OTLF and that xanthine dehydrogenase (XDH) is the key regulatory factor. Receiver operating characteristic (ROC) analysis indicated that 17 metabolites, including uric acid, were found with an AUC value of over 0.7. CONCLUSION: Uric acid might be the potential biomarker for OTLF and play an important role within the detailed pathway. XDH could affect purine metabolism by suppressing the expression of hypoxanthine and xanthine leading to low serum levels of uric acid in OTLF, which could be a focal point in developing new therapeutic methods for OTLF.