Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

脑脊液代谢组学揭示儿童癫痫持续状态的预后生物标志物

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作者:Tianqi Wang, Chunpei Li, Yu Ma, Hao Zhou, Xiaonan Du, Yingfeng Li, Shasha Long, Yifeng Ding, Guoping Lu, Weiming Chen, Yuanfeng Zhou, Lifei Yu, Ji Wang, Yi Wang

Aims

Status epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics.

Conclusions

This study highlighted the prognosis-related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl-glutamine and 3-iodothyronamine with high predictive value was established.

Methods

Ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group (N = 13) with the good outcome group (N = 15) of children with SE. Differentially expressed metabolites were identified using Mann-Whitney U test corrected by Benjamini-Hochberg and partial least squares discriminant analysis (PLS-DA).

Results

The PLS-DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS-DA with R2 Y = 0.992 and Q2 = 0.798). A total of 49 prognosis-related metabolites were identified. Of these metabolites, 20 including glutamyl-glutamine, 3-iodothyronamine, and L-fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl-glutamine and 3-iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis. Conclusions: This study highlighted the prognosis-related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl-glutamine and 3-iodothyronamine with high predictive value was established.

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