Li Chen, Yuan Xian-Bing, Lu Yi-Cheng, Song Zi-Yue
Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Shizi Street 188, SuZhou, Jiangsu Province, 215006, China.
School of Clinical Medicine, Medical College of Soochow University, SuZhou, Jiangsu Province, 215006, China.
BMC Med Genomics. 2025 Jul 1;18(1):111. doi: 10.1186/s12920-025-02177-6.
Cataracts are one of the most prevalent blinding eye diseases globally, and ferroptosis may be involved in its pathogenesis; however, the precise mechanisms remain unclear. We therefore aimed to identify ferroptosis-related genes (FRGs) related to cataracts and assess their causal association.
We downloaded two gene expression profile datasets of patients with cataracts and gathered the FRGs from the MSigDB and GeneCards databases. This allowed us to find the ferroptosis-related differentially expressed genes (FRDEGs). The potential functions of these FRDEGs were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was established, and hub genes were screened. Additionally, potential diagnostic markers were identified by RT-PCR validation. Finally, a Mendelian randomization (MR) study was performed to ascertain the causal impact of FRDEGs on cataracts.
Nineteen FRDEGs were identified by overlapping DEGs with FRGs. GO, KEGG and GSEA showed that the FRDEGs were associated with oxidative stress, IL17 signaling pathway, and glutathione metabolism. Nine hub genes were identified using the PPI network and five algorithms in Cytoscape. The RT-PCR results validated TIGAR, IL6, ATF3, and TNFAIP3 as potential biomarkers.
TIGAR and IL6 were identified to be causally associated with cataracts. Inverse variance weighting revealed that TIGAR decreased the risk of cataracts, whereas IL6 increased the risk of cataract. Our research identified ferroptosis-related hub genes in cataracts, providing valuable insights for pre-symptomatic diagnosis and contributing to our understanding of the molecular mechanisms of cataract risk genes.
白内障是全球最常见的致盲眼病之一，铁死亡可能参与其发病机制；然而，确切机制仍不清楚。因此，我们旨在鉴定与白内障相关的铁死亡相关基因（FRGs）并评估它们的因果关联。
我们下载了两个白内障患者的基因表达谱数据集，并从MSigDB和GeneCards数据库收集了FRGs。这使我们能够找到铁死亡相关的差异表达基因（FRDEGs）。使用京都基因与基因组百科全书（KEGG）、基因本体论（GO）和基因集富集分析（GSEA）探索这些FRDEGs的潜在功能。建立了蛋白质-蛋白质相互作用（PPI）网络，并筛选了枢纽基因。此外，通过RT-PCR验证鉴定潜在的诊断标志物。最后，进行了孟德尔随机化（MR）研究以确定FRDEGs对白内障的因果影响。
通过将差异表达基因与FRGs重叠鉴定出19个FRDEGs。GO、KEGG和GSEA表明，FRDEGs与氧化应激、IL17信号通路和谷胱甘肽代谢有关。使用Cytoscape中的PPI网络和五种算法鉴定出九个枢纽基因。RT-PCR结果验证了TIGAR、IL6、ATF3和TNFAIP3作为潜在的生物标志物。
TIGAR和IL6被确定与白内障存在因果关联。逆方差加权显示，TIGAR降低了患白内障的风险，而IL6增加了患白内障的风险。我们的研究鉴定了白内障中铁死亡相关的枢纽基因，为症状前诊断提供了有价值的见解，并有助于我们理解白内障风险基因的分子机制。
