基于超高效液相色谱-质谱联用的血清代谢组学在难治性肿瘤性骨软化症早期诊断中的应用：一项病例对照研究。

Ultra-High Performance Liquid Chromatography-Mass Spectrometry-based Serum Metabolomics for Early Diagnosis of Refractory Tumor-induced Osteomalacia: A Case-control Study.

机构信息

Department of Endocrinology, Key Laboratory of Endocrinology, National Commission of Health, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

出版信息

J Clin Endocrinol Metab. 2023 Jul 14;108(8):2016-2023. doi: 10.1210/clinem/dgad034.

DOI:10.1210/clinem/dgad034

PMID:36718510

Abstract

CONTEXT

Nearly 20% patients with tumor-induced osteomalacia (TIO) experienced recurrence or nonrecovery after surgery. Serum fibroblast growth factor 23 and phosphate concentrations are not sufficient for prognosis in such cases. Despite its importance for understanding of prognosis and underlying pathogenesis, the alteration of systemic metabolism in refractory TIO remains unclear.

OBJECTIVE

We aimed to find the metabolomic characteristics of refractory TIO and establish a novel predictive model for early discriminating refractory TIO based on their serum metabolomics.

DESIGN AND SETTING

Cross-section study for comparison of metabolomic profile between TIO and normal control and longitudinal study for identifying prognostic model.

METHODS

Based on liquid chromatography-tandem mass spectrometry, we analyzed the global metabolomes of preoperative sera from 86 samples (32 TIO recovery patients, 11 nonremission patients, and 43 matched controls). Statistical analyses, pathway enrichment, and receiver operating characteristic analysis were performed to identified and evaluate potential markers.

RESULTS

Sparse partial least squares discriminant analysis indicated a clear separation of metabolomic profiles between healthy controls (HC) and TIO patients. The serum metabolites altered in different prognostic groups. L-pipecolic acid, 2-dodecylbenzenesulfonic acid, and 2-deoxygalactopyranose were the top 3 metabolites that were significantly perturbed. A combination of L-pipecolic acid and 2-dodecylbenzenesulfonic acid demonstrated a high-performance panel for TIO prognosis evaluated by random forest algorithm (area under the curve = 0.921, 95% CI, 0.787-0.995).

CONCLUSIONS

We investigate the global metabolomes of refractory TIO and identify potential prognostic biomarkers preliminarily. A high sensitivity and specificity panel were identified as promising discriminating predictors, which need to be verified in more patients. This work may demonstrate novel insights into TIO prognosis and pathogenesis.

摘要

背景

近 20%的肿瘤性骨软化症（TIO）患者在手术后会出现复发或未缓解。在这种情况下，血清成纤维细胞生长因子 23 和磷酸盐浓度不足以用于预测预后。尽管对于理解预后和潜在发病机制很重要，但难治性 TIO 中的全身代谢改变仍不清楚。

目的

我们旨在寻找难治性 TIO 的代谢组学特征，并基于其血清代谢组学建立一种新的预测模型，以早期鉴别难治性 TIO。

设计和设置

用于比较 TIO 和正常对照代谢组学图谱的横断面研究和用于确定预后模型的纵向研究。

方法

基于液相色谱-串联质谱法，我们分析了 86 例术前血清的全代谢组（32 例 TIO 缓解患者、11 例未缓解患者和 43 例匹配对照）。采用稀疏偏最小二乘判别分析、通路富集和受试者工作特征分析来识别和评估潜在标志物。

结果

稀疏偏最小二乘判别分析表明，健康对照（HC）和 TIO 患者之间的代谢组学图谱有明显的分离。不同预后组的血清代谢物发生改变。L-哌啶酸、2-十二烷基苯磺酸和 2-脱氧半乳糖吡喃糖是受干扰最大的前 3 种代谢物。L-哌啶酸和 2-十二烷基苯磺酸的组合通过随机森林算法评估 TIO 预后具有较高的性能（曲线下面积=0.921，95%置信区间，0.787-0.995）。