Jiang Han-Tao, Shen Li-Ping, Pang Meng-Qi, Wu Min-Jiao, Li Jiang, Gong Wei-Jie, Jin Gang, Zhu Rang-Teng
Department of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, China.
Department of Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical, Taizhou, Zhejiang, China.
Front Immunol. 2025 Jul 16;16:1559422. doi: 10.3389/fimmu.2025.1559422. eCollection 2025.
Idiopathic 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.
Total 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).
, , , , and were identified as biomarkers for FS. The nomogram constructed based on them had a good predictive value for the occurrence of FS. Except for , the other four genes were upregulated in FS samples, and the expression of , , and 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; generally displayed a negative correlation, while the other four genes were generally positively correlated.
This study established a link between FS biomarkers that have strong diagnostic potential and specific immune responses, highlighting possible targets for diagnosing and treating FS.
特发性冻结肩（FS）可导致日常活动困难，并严重影响生活质量。早期诊断和治疗有助于缓解症状并恢复肩部功能。因此，我们旨在从转录组学角度探索FS的诊断生物标志物和潜在机制。
从15例FS患者和11例对照的组织样本中提取总RNA。首先，我们进行了差异表达分析、加权基因共表达网络分析（WGCNA），并使用了cytoHubba插件，辅以两种机器学习算法、受试者工作特征（ROC）分析和表达水平评估来识别FS的生物标志物。随后，基于这些生物标志物构建了列线图。此外，我们进行了富集和免疫浸润分析，以探索与这些生物标志物相关的机制。最后，我们通过逆转录定量聚合酶链反应（RT-qPCR）在临床水平上确认了生物标志物的表达模式。
[具体基因名称1]、[具体基因名称2]、[具体基因名称3]、[具体基因名称4]和[具体基因名称5]被鉴定为FS的生物标志物。基于它们构建的列线图对FS的发生具有良好的预测价值。除了[具体基因名称1]外，其他四个基因在FS样本中上调，并且在RT-qPCR中也观察到[具体基因名称2]、[具体基因名称3]和[具体基因名称4]的表达显著上调。此外，这些基因在“细胞外基质受体相互作用”和 “溶酶体” 等途径中发挥重要作用。我们还发现，11种免疫细胞的浸润丰度在FS样本中显著上调，并且它们之间呈正相关。我们的生物标志物与这些免疫细胞显示出强烈的相关性；[具体基因名称1]通常呈负相关，而其他四个基因通常呈正相关。
本研究建立了具有强大诊断潜力的FS生物标志物与特定免疫反应之间的联系，突出了FS诊断和治疗的可能靶点。
