Development and validation of potential molecular subtypes and signatures of thyroid eye disease based on...

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.