Zhu Jing, Zhu Shu, Liu Bin, Zheng Xin, Yin Xiaofei, Pu Lingling, Yang Jing
J Endocrinol. 2025 Mar 14;265(2). doi: 10.1530/JOE-24-0362. Print 2025 May 1.
Thyroid eye disease (TED) features immune infiltration and metabolic dysregulation. Understanding these processes and identifying potential biomarkers are crucial for improving diagnosis and treatment. To this end, immune cell infiltration was analyzed and gene set variation analysis (GSVA) was conducted on the GSE58331 dataset to identify differences between TED and normal tissues. Differentially expressed genes were identified using GSE58331 and GSE105149. Subsequently, a prediction model (TEDML) was developed by combining 113 machine learning algorithms to identify key biomarkers. In addition, enrichment analyses were performed to understand biological functions and pathways involved in TED, and drug sensitivity analyses were conducted to identify potential therapeutic agents. Immune infiltration analysis revealed higher levels of CD4+ Tem, CD4+ Tcm, NKT, NK cells and neutrophils in TED patients compared to controls, with lower levels of macrophages M1 and M2. GSVA indicated significant enrichment in immune-related processes and metabolic pathways. The TEDML model, constructed from the Stepglm[forward] algorithm, demonstrated high accuracy (area under curve of 1 on the training set, 0.893 in validation set), identifying six key genes (CSF3R, ALDH1A1, MXRA5, VSIG4, DPP4 and MDH1). Drug sensitivity analysis suggested that azathioprine and methylprednisolone might be effective at different stages of TED, with CSF3R as a potential therapeutic target. Overall, the TEDML model is accurate and reliable, and the identification of CSF3R as a key biomarker and its correlation with drug sensitivity offers new insights into targeted therapy for TED.
甲状腺眼病(TED)具有免疫浸润和代谢失调的特征。了解这些过程并识别潜在的生物标志物对于改善诊断和治疗至关重要。为此,对免疫细胞浸润进行了分析,并对GSE58331数据集进行了基因集变异分析(GSVA),以确定TED与正常组织之间的差异。使用GSE58331和GSE105149鉴定了差异表达基因。随后,通过结合113种机器学习算法开发了一种预测模型(TEDML),以识别关键生物标志物。此外,进行了富集分析以了解TED涉及的生物学功能和途径,并进行了药物敏感性分析以识别潜在的治疗药物。免疫浸润分析显示,与对照组相比,TED患者的CD4 + Tem、CD4 + Tcm、NKT、NK细胞和中性粒细胞水平更高,而巨噬细胞M1和M2水平更低。GSVA表明免疫相关过程和代谢途径有显著富集。由Stepglm[forward]算法构建的TEDML模型显示出高准确性(训练集曲线下面积为1,验证集为0.893),识别出六个关键基因(CSF3R、ALDH1A1、MXRA5、VSIG4、DPP4和MDH1)。药物敏感性分析表明,硫唑嘌呤和甲泼尼龙可能在TED的不同阶段有效,CSF3R作为潜在的治疗靶点。总体而言,TEDML模型准确可靠,将CSF3R鉴定为关键生物标志物及其与药物敏感性的相关性为TED的靶向治疗提供了新的见解。