Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder

BackgroundIdiopathic frozen shoulder (FS) can lead to difficulties in daily activities and significantly impact the quality of life. Early diagnosis and treatment can help alleviate symptoms and restore shoulder function. Therefore, we aimed to explore the diagnostic biomarkers and potential mechani...

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Main Authors: Han-tao Jiang, Li-ping Shen, Meng-Qi Pang, Min-jiao Wu, Jiang Li, Wei-jie Gong, Gang Jin, Rang-teng Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559422/full
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author Han-tao Jiang
Li-ping Shen
Meng-Qi Pang
Min-jiao Wu
Jiang Li
Wei-jie Gong
Gang Jin
Rang-teng Zhu
author_facet Han-tao Jiang
Li-ping Shen
Meng-Qi Pang
Min-jiao Wu
Jiang Li
Wei-jie Gong
Gang Jin
Rang-teng Zhu
author_sort Han-tao Jiang
collection DOAJ
description BackgroundIdiopathic frozen shoulder (FS) can lead to difficulties in daily activities and significantly impact the quality of life. Early diagnosis and treatment can help alleviate symptoms and restore shoulder function. Therefore, we aimed to explore the diagnostic biomarkers and potential mechanisms of FS from a transcriptomics perspective.MethodsTotal RNA was extracted from tissue samples of 15 FS and 11 controls. At the outset, we conducted differential expression analysis, weighted gene co-expression network analysis (WGCNA), and utilized the cytoHubba plugin, complemented by two machine learning algorithms, receiver operating characteristic (ROC) analysis, and expression level evaluation to identify biomarkers for FS. Subsequently, a nomogram was constructed based on the biomarkers. Additionally, we conducted enrichment and immune infiltration analyses to explore the mechanisms associated with these biomarkers. Finally, we confirmed the expression patterns of the biomarkers at the clinical level through reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsSNAI1, TWIST1, COL1A1, TUBB2B, and DCN were identified as biomarkers for FS. The nomogram constructed based on them had a good predictive value for the occurrence of FS. Except for DCN, the other four genes were upregulated in FS samples, and the expression of SNAI1, TWIST1, and TUBB2B was also observed to be significantly upregulated in RT-qPCR. Moreover, these genes played important roles in pathways such as “ECM receptor interaction” and “lysosome”. We also found that the infiltration abundances of 11 types of immune cells were significantly upregulated in the FS samples, and they were positively correlated with each other. Our biomarkers showed strong correlations with these immune cells; DCN generally displayed a negative correlation, while the other four genes were generally positively correlated.ConclusionThis study established a link between FS biomarkers that have strong diagnostic potential and specific immune responses, highlighting possible targets for diagnosing and treating FS.
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spelling doaj-art-489ae891cd8e4edba88b8a1f0b6d72062025-08-20T02:39:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15594221559422Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulderHan-tao Jiang0Li-ping Shen1Meng-Qi Pang2Min-jiao Wu3Jiang Li4Wei-jie Gong5Gang Jin6Rang-teng Zhu7Department of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Operating Room, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, ChinaBackgroundIdiopathic frozen shoulder (FS) can lead to difficulties in daily activities and significantly impact the quality of life. Early diagnosis and treatment can help alleviate symptoms and restore shoulder function. Therefore, we aimed to explore the diagnostic biomarkers and potential mechanisms of FS from a transcriptomics perspective.MethodsTotal RNA was extracted from tissue samples of 15 FS and 11 controls. At the outset, we conducted differential expression analysis, weighted gene co-expression network analysis (WGCNA), and utilized the cytoHubba plugin, complemented by two machine learning algorithms, receiver operating characteristic (ROC) analysis, and expression level evaluation to identify biomarkers for FS. Subsequently, a nomogram was constructed based on the biomarkers. Additionally, we conducted enrichment and immune infiltration analyses to explore the mechanisms associated with these biomarkers. Finally, we confirmed the expression patterns of the biomarkers at the clinical level through reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsSNAI1, TWIST1, COL1A1, TUBB2B, and DCN were identified as biomarkers for FS. The nomogram constructed based on them had a good predictive value for the occurrence of FS. Except for DCN, the other four genes were upregulated in FS samples, and the expression of SNAI1, TWIST1, and TUBB2B was also observed to be significantly upregulated in RT-qPCR. Moreover, these genes played important roles in pathways such as “ECM receptor interaction” and “lysosome”. We also found that the infiltration abundances of 11 types of immune cells were significantly upregulated in the FS samples, and they were positively correlated with each other. Our biomarkers showed strong correlations with these immune cells; DCN generally displayed a negative correlation, while the other four genes were generally positively correlated.ConclusionThis study established a link between FS biomarkers that have strong diagnostic potential and specific immune responses, highlighting possible targets for diagnosing and treating FS.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559422/fullfrozen shoulderimmune infiltrationtranscriptomicsbioinformaticsnomogram
spellingShingle Han-tao Jiang
Li-ping Shen
Meng-Qi Pang
Min-jiao Wu
Jiang Li
Wei-jie Gong
Gang Jin
Rang-teng Zhu
Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
Frontiers in Immunology
frozen shoulder
immune infiltration
transcriptomics
bioinformatics
nomogram
title Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
title_full Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
title_fullStr Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
title_full_unstemmed Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
title_short Identification and validation of biomarkers, construction of diagnostic models, and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
title_sort identification and validation of biomarkers construction of diagnostic models and investigation of immunological infiltration characteristics for idiopathic frozen shoulder
topic frozen shoulder
immune infiltration
transcriptomics
bioinformatics
nomogram
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1559422/full
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