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

Abstract

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.

Clinical Risk Factors for Thoracic Ossification of the Ligamentum Flavum: A Cross-Sectional Study Based on Spinal Thoracic Three-Dimensional Computerized Tomography

“… 26 Li et al used metabolomics and transcriptomics to identify the molecular mechanism and diagnostic biomarkers in TOLF, and the result shows that uric acid might be the potential biomarker for TOLF and play an important role in the detailed pathway. 27 However, there were only 25 patients with TOLF and 23 healthy volunteers included in the research. Thus, the relatively small sample size may cause bias of result.…”

Thoracic spondylotic myelopathy in diffuse idiopathic skeletal hyperostosis: a comparative study

“…However, recent research on the etiology, early screening and diagnosis of thoracic stenosis is gradually revealing the progression of TSS. Stimulation of mechanical stress may be one of the driving factors [ 6 , 7 ]. Quantitative measurement by CT or Magnetic Resonance Imaging (MRI) can help us to predict the operative risk and postoperative recovery of TSS to a certain extent [ 8 ].…”

Biomarker Research Approach to the Pathogenesis of Ossification of the Spinal Ligament: A Review

“…They identified nine spots that were differentially expressed in the sera of OPLL patients as follows: PRO2675; human serum albumin in a complex with myristic acid and triiodobenzoic acid; an unknown protein; chain B of the crystal structure of deoxy human hemoglobin beta 6; pro-apolipoprotein; ALB protein; retinol-binding protein; and chain A of human serum albumin mutant R218h complexed with thyroxine (3,3′,5,5′; tetraiodo-L-thyronine) were upregulated, whereas the 1-microglobulin/bikunin precursor was downregulated 17) . A Chinese group analyzed diagnostic biomarkers in blood samples of thoracic OLF patients using metabolomics and transcriptomics 18) . The authors included 25 patients with OLF and recruited 23 healthy volunteers for the control group.…”