Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning

Abstract Background Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly contributes to global disability. Glycolysis, a fundamental process in cellular energy metabolism, is particularly vital for chondrocytes in OA. This study aims to explore the intrinsic relationship...

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Main Authors: Wangnan Mao, Zhengsheng Bao, Bingbing Zhang, Lianguo Wu
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-025-06072-9
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author Wangnan Mao
Zhengsheng Bao
Bingbing Zhang
Lianguo Wu
author_facet Wangnan Mao
Zhengsheng Bao
Bingbing Zhang
Lianguo Wu
author_sort Wangnan Mao
collection DOAJ
description Abstract Background Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly contributes to global disability. Glycolysis, a fundamental process in cellular energy metabolism, is particularly vital for chondrocytes in OA. This study aims to explore the intrinsic relationship between glycolysis-related genes (GRGs) and OA. Methods We incorporated three publicly available datasets from the Gene Expression Omnibus (GEO) database, which included 64 OA samples and 34 normal controls. By utilizing differential expression analysis, weighted gene co-expression network analysis, protein-protein interaction networks, and machine learning methods, we identified three diagnostic biomarkers of OA patients. The expression levels of these biomarkers were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC). Additionally, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory interactions. Results Through bioinformatics and machine learning approaches, three glycolysis-related biomarkers—HMGB2, SLC7A5, and ADM—were identified. The diagnostic model based on these GRGs demonstrated high predictive accuracy, with an AUC of 0.92 in the training set and 0.85 in the validation set. Subsequently, qRT-PCR and IHC confirmed the differential expression of hub genes in human cartilage samples. Furthermore, immunocyte infiltration analysis revealed distinct immune cell infiltration profiles between OA and HC groups. Notably, lncRNA XIST was found to regulate all three biomarkers, indicating its potential as a therapeutic target for OA. Conclusion This study provides novel insights into the role of glycolysis in OA pathogenesis and highlights its potential as a target for diagnosis, prevention, and treatment strategies.
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institution Kabale University
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publishDate 2025-07-01
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spelling doaj-art-c93e9d4973a14d4c9280ea8d7d815bc82025-08-20T04:03:00ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-07-0120111610.1186/s13018-025-06072-9Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learningWangnan Mao0Zhengsheng Bao1Bingbing Zhang2Lianguo Wu3The Second Clinical College, Zhejiang Chinese Medical UniversityDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Zhejiang, Chinese Medical UniversityThe Second Clinical College, Zhejiang Chinese Medical UniversityThe Second Clinical College, Zhejiang Chinese Medical UniversityAbstract Background Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly contributes to global disability. Glycolysis, a fundamental process in cellular energy metabolism, is particularly vital for chondrocytes in OA. This study aims to explore the intrinsic relationship between glycolysis-related genes (GRGs) and OA. Methods We incorporated three publicly available datasets from the Gene Expression Omnibus (GEO) database, which included 64 OA samples and 34 normal controls. By utilizing differential expression analysis, weighted gene co-expression network analysis, protein-protein interaction networks, and machine learning methods, we identified three diagnostic biomarkers of OA patients. The expression levels of these biomarkers were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC). Additionally, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory interactions. Results Through bioinformatics and machine learning approaches, three glycolysis-related biomarkers—HMGB2, SLC7A5, and ADM—were identified. The diagnostic model based on these GRGs demonstrated high predictive accuracy, with an AUC of 0.92 in the training set and 0.85 in the validation set. Subsequently, qRT-PCR and IHC confirmed the differential expression of hub genes in human cartilage samples. Furthermore, immunocyte infiltration analysis revealed distinct immune cell infiltration profiles between OA and HC groups. Notably, lncRNA XIST was found to regulate all three biomarkers, indicating its potential as a therapeutic target for OA. Conclusion This study provides novel insights into the role of glycolysis in OA pathogenesis and highlights its potential as a target for diagnosis, prevention, and treatment strategies.https://doi.org/10.1186/s13018-025-06072-9OsteoarthritisGlycolysisBioinformatics analysisMachine learning algorithmsImmune cells
spellingShingle Wangnan Mao
Zhengsheng Bao
Bingbing Zhang
Lianguo Wu
Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
Journal of Orthopaedic Surgery and Research
Osteoarthritis
Glycolysis
Bioinformatics analysis
Machine learning algorithms
Immune cells
title Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
title_full Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
title_fullStr Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
title_full_unstemmed Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
title_short Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
title_sort construction of a glycolysis related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning
topic Osteoarthritis
Glycolysis
Bioinformatics analysis
Machine learning algorithms
Immune cells
url https://doi.org/10.1186/s13018-025-06072-9
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AT bingbingzhang constructionofaglycolysisrelateddiagnosticmodelforosteoarthritisthroughintegratedbioinformaticsanalysisandmachinelearning
AT lianguowu constructionofaglycolysisrelateddiagnosticmodelforosteoarthritisthroughintegratedbioinformaticsanalysisandmachinelearning