Wu Zixuan, Peng Jun, Long Xi, Tan Kang, Yao Xiaolei, Peng Qinghua
Hunan University of Chinese Medicine, Changsha, Hunan Province, 410208, China.
The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, 410007, China.
BMC Pharmacol Toxicol. 2025 Mar 10;26(1):53. doi: 10.1186/s40360-025-00880-9.
Thyroid eye disease (TED) is an autoimmune inflammatory disorder of the orbit, associated with a range of potential clinical sequelae. Tumor cells in TED overexpress pro-angiogenic factors, driving the formation of heterogeneous and immature neovascularization. This dysregulated angiogenesis often leads to a hypoxic microenvironment due to insufficient perfusion. Despite its importance, the role of angiogenesis-related genes (ARGs) in TED pathophysiology remains poorly understood.
To bridge this knowledge gap, our study aimed to identify and validate ARGs implicated in TED using a comprehensive bioinformatics strategy. By intersecting differential gene expression analyses with a curated list of 103 known ARGs, we aimed to pinpoint those with potential roles in TED. Advanced methodologies, including GSEA and GSVA, facilitated an in-depth exploration of the biological functions and pathways associated with these ARGs. Further refinement through Lasso regression and SVM-RFE enabled the identification of key hub genes and the evaluation of their diagnostic potential for TED. Additionally, we investigated the relationship between these hub ARGs and relevant clinical parameters. To corroborate our findings, we analyzed expression data from datasets GSE58331 and GSE105149, focusing on the six ARGs identified as potentially crucial to TED pathology.
Our investigation unveiled six ARGs (CRIP2, DUSP1, CTSL, DOCK5, ERAP1, SCG2) as intimately connected to TED. Functional analyses highlighted their involvement in processes such as response to ameboidal-type cell migration, epithelial cell migration, epithelium migration. Importantly, the diagnostic capabilities of these ARGs demonstrated promising efficacy in distinguishing TED from non-affected states.
This study identifies six ARGs as novel biomarker candidates for TED, elucidating their potential roles in the disease's pathogenesis.
甲状腺眼病（TED）是一种眼眶自身免疫性炎症性疾病，伴有一系列潜在的临床后遗症。TED中的肿瘤细胞过度表达促血管生成因子，驱动异质性和不成熟的新生血管形成。这种失调的血管生成由于灌注不足，常导致缺氧微环境。尽管血管生成相关基因（ARGs）很重要，但其在TED病理生理学中的作用仍知之甚少。
为了填补这一知识空白，我们的研究旨在使用全面的生物信息学策略来识别和验证与TED相关的ARGs。通过将差异基因表达分析与103个已知ARGs的精选列表相交，我们旨在找出那些在TED中具有潜在作用的基因。包括基因集富集分析（GSEA）和基因集变异分析（GSVA）在内的先进方法，有助于深入探索与这些ARGs相关的生物学功能和途径。通过套索回归和支持向量机递归特征消除（SVM-RFE）进一步优化，能够识别关键的枢纽基因，并评估其对TED的诊断潜力。此外，我们研究了这些枢纽ARGs与相关临床参数之间的关系。为了证实我们的发现，我们分析了数据集GSE58331和GSE105149的表达数据，重点关注被确定为对TED病理可能至关重要的六个ARGs。
我们的研究揭示了六个与TED密切相关的ARGs（CRIP2、DUSP1、CTSL、DOCK5、ERAP1、SCG2）。功能分析突出了它们参与诸如对阿米巴样细胞迁移的反应、上皮细胞迁移、上皮迁移等过程。重要的是，这些ARGs的诊断能力在区分TED与未受影响状态方面显示出有前景的效果。
本研究确定了六个ARGs作为TED的新型生物标志物候选物，阐明了它们在疾病发病机制中的潜在作用。
