Ma Qintao, Hai Yuanping, Shen Jie
Department of Endocrinology and Metabolism, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, China.
Immun Inflamm Dis. 2024 Dec;12(12):e70093. doi: 10.1002/iid3.70093.
Thyroid-associated ophthalmopathy (TAO) is one of the most complex autoimmune diseases in endocrinology areas. Autophagy-related genes may be involved in the pathophysiology of TAO. This study aims to reveal key genes associated with autophagy in the pathogenesis and the potential diagnostic markers for TAO.
We obtained autophagy-related differential genes (AR-DEGs) and their expression in TAO patients and controls. Gene ontology analysis (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to perform the enrichment analysis of AR-DEGs. LASSO regression, support vector machine recursive feature elimination, and random forest were performed to screen for disease signature genes (DSGs), which were further validated in another independent validation dataset. We used the receiver operating characteristic for the evaluation of the diagnostic efficacy of DSGs and also established a nomogram. The relative proportion of immune infiltration was calculated using the CIBERSORT algorithm, and the relationship between the identified gene markers and the level of infiltrating immune cells was explored.
We identified 24 AR-DEGs, which were primarily enriched in cellular catabolic regulation, autophagosome membrane, and ubiquitin protein ligase binding in GO analysis, while KEGG analysis highlighted autophagy as the main enriched pathway. Six DSGs were identified by three algorithms. They were validated in another independent validation dataset. The combined six-gene model also showed good diagnostic efficacy (AUC = 0.948). We further plotted the nomogram with better diagnostic efficacy. Immuno-infiltration analysis and correlation analysis demonstrated that six DSGs were significantly correlated with the infiltrating immune cells.
We identified several biological processes and pathways for the enrichment of AR-DEGs. Six DSGs were identified, which showed great potential to become critical molecules in the diagnosis of TAO, and these DSGs showed a correlation with infiltrating immune cells.
甲状腺相关性眼病（TAO）是内分泌领域最复杂的自身免疫性疾病之一。自噬相关基因可能参与TAO的病理生理过程。本研究旨在揭示发病机制中与自噬相关的关键基因以及TAO的潜在诊断标志物。
我们获取了TAO患者和对照组的自噬相关差异基因（AR-DEGs）及其表达情况。采用基因本体分析（GO）和京都基因与基因组百科全书（KEGG）分析对AR-DEGs进行富集分析。进行套索回归、支持向量机递归特征消除和随机森林分析以筛选疾病特征基因（DSGs），并在另一个独立的验证数据集中对其进行进一步验证。我们使用受试者工作特征曲线评估DSGs的诊断效能，并建立了列线图。使用CIBERSORT算法计算免疫浸润的相对比例，并探讨所确定的基因标志物与浸润免疫细胞水平之间的关系。
我们鉴定出24个AR-DEGs，在GO分析中主要富集于细胞分解代谢调节、自噬体膜和泛素蛋白连接酶结合，而KEGG分析突出显示自噬是主要的富集途径。通过三种算法鉴定出6个DSGs。它们在另一个独立的验证数据集中得到了验证。六基因联合模型也显示出良好的诊断效能（AUC = 0.948）。我们进一步绘制了诊断效能更好的列线图。免疫浸润分析和相关性分析表明，6个DSGs与浸润免疫细胞显著相关。
我们鉴定出了几个AR-DEGs富集的生物学过程和途径。鉴定出的6个DSGs在TAO诊断中具有成为关键分子的巨大潜力，并且这些DSGs与浸润免疫细胞存在相关性。
