Yu Cai-Han, Wu Cai-Xia, Li Dai, Gong Lan-Lan, Lyu Xu-Dong, Yang Jie
Department of Ophthalmology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning 437100, Hubei Province, China.
School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, Hubei Province, 437100, China.
Int J Ophthalmol. 2024 Aug 18;17(8):1411-1417. doi: 10.18240/ijo.2024.08.04. eCollection 2024.
To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression.
Hypoxia-related differentially expressed genes (DEGs) were identified from the GSE60436 and GSE102485 datasets, followed by gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Potential candidate drugs were screened using the CMap database. Subsequently, a protein-protein interaction (PPI) network was constructed to identify hypoxia-related hub genes. A nomogram was generated using the rms R package, and the correlation of hub genes was analyzed using the Hmisc R package. The clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve (ROC) curves. Finally, a hypoxia-related miRNA-transcription factor (TF)-Hub gene network was constructed using the NetworkAnalyst online tool.
Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified, such as ruxolitinib, meprylcaine, and deferiprone. In addition, 8 hub genes were also identified: glycogen phosphorylase muscle associated (), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (), enolase 3 (), aldolase fructose-bisphosphate C (), phosphoglucomutase 2 (), enolase 2 (), phosphoglycerate mutase 2 (), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (). Based on hub gene predictions, the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs, 77 TFs, and hub genes. The results of ROC showed that the except for , the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance.
, , , , , , , and are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.
预防糖尿病视网膜病变（DR）患者的新生血管形成并部分控制疾病进展。
从GSE60436和GSE102485数据集中鉴定缺氧相关差异表达基因（DEG），随后进行基因本体（GO）功能注释和京都基因与基因组百科全书（KEGG）通路富集分析。使用CMap数据库筛选潜在的候选药物。随后，构建蛋白质-蛋白质相互作用（PPI）网络以鉴定缺氧相关的枢纽基因。使用rms R软件包生成列线图，并使用Hmisc R软件包分析枢纽基因的相关性。通过比较疾病组和正常组之间的表达水平并构建受试者工作特征曲线（ROC）来验证枢纽基因的临床意义。最后，使用NetworkAnalyst在线工具构建缺氧相关的miRNA-转录因子（TF）-枢纽基因网络。
共鉴定出48个缺氧相关的DEG，并筛选出10种与上调的缺氧相关基因具有相互作用关系的潜在候选药物，如鲁索替尼、美普卡因和去铁酮。此外，还鉴定出8个枢纽基因：糖原磷酸化酶肌肉相关（）、生精甘油醛-3-磷酸脱氢酶（）、烯醇化酶3（）、果糖二磷酸醛缩酶C（）、磷酸葡萄糖变位酶2（）、烯醇化酶2（）、磷酸甘油酸变位酶2（）和6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶3（）。基于枢纽基因预测，miRNA-TF-枢纽基因网络揭示了163个miRNA、77个TF和枢纽基因之间的复杂相互作用。ROC结果显示，除了（此处原文缺失具体基因名）外，其他7个枢纽基因的曲线下面积（AUC）值均大于0.758，表明它们具有良好的诊断性能。
（此处原文缺失具体基因名）、（此处原文缺失具体基因名）、（此处原文缺失具体基因名）、（此处原文缺失具体基因名）、（此处原文缺失具体基因名）、（此处原文缺失具体基因名）、（此处原文缺失具体基因名）和（此处原文缺失具体基因名）是DR中的枢纽基因，且缺氧相关的枢纽基因表现出良好的诊断性能。
