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基于 LC-MS 的慢性硬脑膜下血肿尿液代谢组学分析用于生物标志物发现。

LC-MS-based urine metabolomics analysis of chronic subdural hematoma for biomarker discovery.

机构信息

Core Instrument Facility, Institute of Basic Medical Sciences, School of Basic Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Proteomics Clin Appl. 2024 Jan;18(1):e2200107. doi: 10.1002/prca.202200107. Epub 2023 Sep 11.

DOI:10.1002/prca.202200107
PMID:37697649
Abstract

BACKGROUND

Chronic subdural hematoma (CSDH) is one of the most common neurosurgical diseases with atypical manifestations. The aim of this study was to utilize urine metabolomics to explore potential biomarkers for the diagnosis and prognosis of CSDH.

METHODS

Seventy-seven healthy controls and ninety-two patients with CSDH were enrolled in our study. In total, 261 urine samples divided into the discovery group and validation group were analyzed by LC-MS. The statistical analysis and functional annotation were applied to discover potential biomarker panels and altered metabolic pathways.

RESULTS

A total of 53 differential metabolites were identified in this study. And the urinary metabolic profiles showed apparent separation between patients and controls. Further functional annotation showed that the differential metabolites were associated with lipid metabolism, fatty acid metabolism, amino acid metabolism, biotin metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions. Moreover, one panel of Capryloylglycine, cis-5-Octenoic acid, Ethisterone, and 5,6-DiHETE showed good predictive performance in the diagnosis of CSDH, with an AUC of 0.89 in discovery group and an AUC of 0.822 in validation group. Another five metabolites (Trilobinol, 3'-Hydroxyropivacaine, Ethisterone, Arginyl-Proline, 5-alpha-Dihydrotestosterone glucuronide) showed the levels of them returned to a healthy state after surgery, showing good possibility to monitor the recovery of CSDH patients.

CONCLUSION AND CLINICAL RELEVANCE

The findings of the study revealed urine metabolomic differences between CSDH and controls. The potentially diagnostic and prognostic biomarker panels of urine metabolites were established, and functional analysis demonstrated deeper metabolic disorders of CSDH, which might conduce to improve early diagnose of CSDH clinically.

摘要

背景

慢性硬脑膜下血肿(CSDH)是最常见的神经外科疾病之一,具有非典型表现。本研究旨在利用尿液代谢组学探索 CSDH 诊断和预后的潜在生物标志物。

方法

本研究纳入了 77 名健康对照者和 92 名 CSDH 患者。共分析了 261 份尿液样本,分为发现组和验证组,采用 LC-MS 进行分析。应用统计分析和功能注释来发现潜在的生物标志物组合和改变的代谢途径。

结果

本研究共鉴定出 53 种差异代谢物。尿液代谢谱显示患者和对照组之间有明显的分离。进一步的功能注释表明,差异代谢物与脂质代谢、脂肪酸代谢、氨基酸代谢、生物素代谢、甾体激素生物合成以及戊糖和葡萄糖醛酸转化有关。此外,Capryloylglycine、cis-5-Octenoic acid、Ethisterone 和 5,6-DiHETE 组成的一个面板在 CSDH 的诊断中具有良好的预测性能,在发现组中的 AUC 为 0.89,在验证组中的 AUC 为 0.822。另外 5 种代谢物(三萜烯醇、3'-羟基罗哌卡因、Ethisterone、精氨酸-脯氨酸、5-α-二氢睾酮葡萄糖醛酸)术后水平恢复至健康状态,表明其具有监测 CSDH 患者康复的良好可能性。

结论和临床相关性

本研究揭示了 CSDH 与对照组之间的尿液代谢组学差异。建立了尿液代谢物潜在的诊断和预后生物标志物组合,功能分析表明 CSDH 存在更深层次的代谢紊乱,这可能有助于临床上提高 CSDH 的早期诊断。

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