Development and validation of potential molecular subtypes and signatures of thyroid eye disease based on angiogenesis-related gene analysis.

IF 2.8 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Zixuan Wu, Jun Peng, Xi Long, Kang Tan, Xiaolei Yao, Qinghua Peng
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: This study identifies six ARGs as novel biomarker candidates for TED, elucidating their potential roles in the disease's pathogenesis.

基于血管生成相关基因分析的甲状腺眼病潜在分子亚型和特征的开发和验证
背景:甲状腺眼病(TED)是一种眼眶自身免疫性炎症性疾病,与一系列潜在的临床后遗症相关。TED肿瘤细胞过度表达促血管生成因子,驱动异质和不成熟新生血管的形成。这种失调的血管生成往往导致缺氧的微环境,由于灌注不足。尽管其重要性,血管生成相关基因(ARGs)在TED病理生理中的作用仍然知之甚少。方法:为了弥补这一知识差距,我们的研究旨在利用综合生物信息学策略识别和验证与TED相关的ARGs。通过将差异基因表达分析与103个已知ARGs的筛选列表相结合,我们旨在确定那些在TED中具有潜在作用的基因。包括GSEA和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Lasso回归和SVM-RFE进一步细化,可以识别关键枢纽基因并评估其诊断TED的潜力。此外,我们还研究了这些中枢ARGs与相关临床参数之间的关系。为了证实我们的发现,我们分析了来自GSE58331和GSE105149数据集的表达数据,重点研究了六个被认为对TED病理可能至关重要的ARGs。结果:我们的研究揭示了6个与TED密切相关的ARGs (CRIP2, DUSP1, CTSL, DOCK5, ERAP1, SCG2)。功能分析强调了它们对变形虫型细胞迁移、上皮细胞迁移、上皮细胞迁移的反应等过程的参与。重要的是,这些ARGs的诊断能力在区分TED和非受影响状态方面显示出有希望的功效。结论:本研究确定了6种ARGs作为新的TED生物标志物候选物,阐明了它们在该疾病发病机制中的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Pharmacology & Toxicology
BMC Pharmacology & Toxicology PHARMACOLOGY & PHARMACYTOXICOLOGY&nb-TOXICOLOGY
CiteScore
4.80
自引率
0.00%
发文量
87
审稿时长
12 weeks
期刊介绍: BMC Pharmacology and Toxicology is an open access, peer-reviewed journal that considers articles on all aspects of chemically defined therapeutic and toxic agents. The journal welcomes submissions from all fields of experimental and clinical pharmacology including clinical trials and toxicology.
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