基于综合生物信息学和孟德尔随机化的原发性开角型青光眼视神经相关生物标志物的鉴定。

Identification of Optic Nerve-Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.

Bengbu Medical University, Bengbu, Anhui, China.

出版信息

Transl Vis Sci Technol. 2024 Aug 1;13(8):21. doi: 10.1167/tvst.13.8.21.

PURPOSE

Glaucoma is the primary cause of permanent vision loss worldwide. However, the pathogenesis of primary open-angle glaucoma (POAG), the main type of glaucoma, has not yet been completely understood.

METHODS

In our study, the POAG cohorts were obtained from the Gene Expression Omnibus (GEO) database (GSE45570). Biomarkers with diagnostic utility for POAG were identified through combining differentially expressed analysis, enrichment analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. The regulatory networks (including a competing endogenous RNA (ceRNA) regulatory network and a small molecule compounds-mRNA network) were created. In addition, the Mendelian randomization (MR) analysis was used to identify exposures causally associated with POAG. Finally, the expression of the biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

The Gene Ontology (GO) items that the differentially expressed genes (DEGs) between POAG and control groups enriched were relevant to light stimulation and DNA methylation. A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients. Besides, the ceRNA regulatory network contained 88 nodes and 93 edges, and a small molecule compounds-mRNA network included 66 nodes and 76 edges. The MR results indicated a causal association between DNA methylation GrimAge acceleration and POAG. Additionally, the results of RT-qPCR revealed that the expression trend of RAB8A was consistent with that of GSE45570.

CONCLUSIONS

Taken together, this study provides three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) for the diagnosis of POAG, providing scientifically valuable insights for further studies of POAG.

TRANSLATIONAL RELEVANCE

Discovering biomarkers that possess diagnostic significance for POAG has the potential to offer new insights into the pathogenesis of POAG and present novel objectives for clinical intervention.

目的

青光眼是全球范围内导致永久性视力丧失的主要原因。然而，原发性开角型青光眼（POAG）的发病机制，即青光眼的主要类型，尚未完全了解。

方法

在我们的研究中，POAG 队列是从基因表达综合数据库（GEO）（GSE45570）中获得的。通过结合差异表达分析、富集分析、机器学习算法和接收者操作特征（ROC）分析，确定具有 POAG 诊断效用的生物标志物。创建了调控网络（包括竞争性内源性 RNA（ceRNA）调控网络和小分子化合物-mRNA 网络）。此外，采用孟德尔随机化（MR）分析来识别与 POAG 有因果关系的暴露。最后，通过实时定量聚合酶链反应（RT-qPCR）验证生物标志物的表达。

结果

POAG 组和对照组之间差异表达基因（DEGs）富集的基因本体论（GO）项目与光刺激和 DNA 甲基化有关。共鉴定出 3 个与光刺激相关的生物标志物（RAB8A、PRG3 和 SMAD3），它们对 POAG 患者具有诊断价值。此外，ceRNA 调控网络包含 88 个节点和 93 个边，小分子化合物-mRNA 网络包含 66 个节点和 76 个边。MR 结果表明 DNA 甲基化 GrimAge 加速与 POAG 之间存在因果关系。此外，RT-qPCR 的结果表明 RAB8A 的表达趋势与 GSE45570 的表达趋势一致。