{"title":"Clinical metabolomics reveals potential diagnostic biomarkers in serum samples from patients with generalized ligamentous laxity.","authors":"Yu Zhang, Xiaochao Hu, Feng Chen, Tongtong Liu, Ping Cai, Shijia Liu, Luning Sun","doi":"10.3389/fmolb.2025.1554936","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Design: </strong>Prospective, observational cohort study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Through identification of serum biomarkers and analysis of metabolic pathways, the current study provided novel insights into GLL pathogenesis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1554936"},"PeriodicalIF":3.9000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162281/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2025.1554936","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: 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.
Design: Prospective, observational cohort study.
Methods: 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.
Results: 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.
Conclusion: Through identification of serum biomarkers and analysis of metabolic pathways, the current study provided novel insights into GLL pathogenesis.
期刊介绍：
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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