Zhang Yu, Hu Xiaochao, Chen Feng, Liu Tongtong, Cai Ping, Liu Shijia, Sun Luning
Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Front Mol Biosci. 2025 May 30;12:1554936. doi: 10.3389/fmolb.2025.1554936. eCollection 2025.
Discovering the potential metabolic alterations underlying generalized ligamentous laxity (GLL) is crucial for identifying new therapeutic targets and improving patient prognosis. Serum metabolites could mirror systemic and local alterations and help understand the metabolic features of GLL. The present work aimed to determine serum biomarkers for GLL diagnosis and to unveil metabolic pathways linked to GLL.
Prospective, observational cohort study.
In this study, serum sample collection was conducted from 65 GLL and 35 healthy control (HC) cases. The obtained specimens were assessed by ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Orthogonal partial least squares-discriminant analysis (OPLS-DA), random forest (RF), binary logistic regression (BLR) and receiver operating characteristic (ROC) analyses were applied to screen and validate biomarkers.
Totally 24 small-molecules were considered differentially expressed metabolites. Of these, hexadecanamide was found to be a specific biomarker for differential diagnosis of GLL, with an area under the ROC curve (AUC) of 0.907. Additionally, the α-linolenic acid and linoleic acid metabolism had the most substantial alteration among various pathways in GLL cases. The altered pathway of α-linolenic acid and linoleic acid metabolism affected bone mineral density and bone metabolism in GLL patients, leading to enhanced inflammation or fracture of the bone and joints. Joint inflammation and dislocation led to systemic ligament relaxation, which induced and aggravated musculoskeletal injury.
Through identification of serum biomarkers and analysis of metabolic pathways, the current study provided novel insights into GLL pathogenesis.
发现全身韧带松弛（GLL）潜在的代谢改变对于确定新的治疗靶点和改善患者预后至关重要。血清代谢物可以反映全身和局部的改变，有助于了解GLL的代谢特征。本研究旨在确定用于GLL诊断的血清生物标志物，并揭示与GLL相关的代谢途径。
前瞻性观察队列研究。
本研究收集了65例GLL患者和35例健康对照（HC）的血清样本。所获得的标本通过超高效液相色谱高分辨率质谱（UPLC-HRMS）进行评估。采用正交偏最小二乘判别分析（OPLS-DA）、随机森林（RF）、二元逻辑回归（BLR）和受试者工作特征（ROC）分析来筛选和验证生物标志物。
共24种小分子被认为是差异表达的代谢物。其中，十六酰胺被发现是GLL鉴别诊断的特异性生物标志物，ROC曲线下面积（AUC）为0.907。此外，α-亚麻酸和亚油酸代谢在GLL病例的各种途径中改变最为显著。α-亚麻酸和亚油酸代谢途径的改变影响了GLL患者的骨密度和骨代谢，导致骨骼和关节的炎症或骨折加重。关节炎症和脱位导致全身韧带松弛，进而诱发和加重肌肉骨骼损伤。
通过血清生物标志物的鉴定和代谢途径的分析，本研究为GLL的发病机制提供了新的见解。
