基于缺氧相关基因的糖尿病视网膜病变关键基因和调控网络:生物信息学分析。

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY International journal of ophthalmology Pub Date : 2024-08-18 eCollection Date: 2024-01-01 DOI:10.18240/ijo.2024.08.04
Cai-Han Yu, Cai-Xia Wu, Dai Li, Lan-Lan Gong, Xu-Dong Lyu, Jie Yang
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引用次数: 0

摘要

方法:从 GSE60436 和 GSE102485 数据集中鉴定缺氧相关差异表达基因(DEGs),然后进行基因本体论(GO)功能注释和京都基因和基因组百科全书(KEGG)通路富集分析。利用 CMap 数据库筛选潜在候选药物。随后,构建了蛋白质-蛋白质相互作用(PPI)网络,以确定与缺氧相关的枢纽基因。使用 rms R 软件包生成了提名图,并使用 Hmisc R 软件包分析了枢纽基因的相关性。通过比较疾病组和正常组的表达水平并构建接收者操作特征曲线(ROC),验证了枢纽基因的临床意义。最后,利用 NetworkAnalyst 在线工具构建了缺氧相关 miRNA-转录因子(TF)-枢纽基因网络:结果:共发现48个与缺氧相关的DEGs,并筛选出10个与上调的缺氧相关基因有相互作用关系的潜在候选药物,如鲁索利替尼 (ruxolitinib)、美普卡因 (meprylcaine) 和去铁酮 (deferiprone)。此外,还发现了 8 个枢纽基因:糖原磷酸化酶肌肉相关(PYGM)、甘油醛-3-磷酸脱氢酶精原细胞(GAPDHS)、烯醇化酶 3(ENO3)、果糖二磷酸醛缩酶 C(ALDOC)、2 (PGM2)、烯醇化酶 2 (ENO2)、磷酸甘油酸突变酶 2 (PGAM2) 和 6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶 3 (PFKFB3)。根据中枢基因预测,miRNA-TF-中枢基因网络揭示了163个miRNA、77个TF和中枢基因之间复杂的相互作用。ROC结果显示,除GAPDHS外,其他7个中枢基因的曲线下面积(AUC)值均大于0.758,表明它们具有良好的诊断性能:结论:PYGM、GAPDHS、ENO3、ALDOC、PGM2、ENO2、PGAM2和PFKFB3是DR的枢纽基因,缺氧相关的枢纽基因具有良好的诊断性能。
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Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes: a bioinformatics analysis.

Aim: To prevent neovascularization in diabetic retinopathy (DR) patients and partially control disease progression.

Methods: 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.

Results: 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 (PYGM), glyceraldehyde-3-phosphate dehydrogenase spermatogenic (GAPDHS), enolase 3 (ENO3), aldolase fructose-bisphosphate C (ALDOC), phosphoglucomutase 2 (PGM2), enolase 2 (ENO2), phosphoglycerate mutase 2 (PGAM2), and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). 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 GAPDHS, the area under curve (AUC) values of the other 7 hub genes were greater than 0.758, indicating their favorable diagnostic performance.

Conclusion: PYGM, GAPDHS, ENO3, ALDOC, PGM2, ENO2, PGAM2, and PFKFB3 are hub genes in DR, and hypoxia-related hub genes exhibited favorable diagnostic performance.

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来源期刊
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期刊介绍: · International Journal of Ophthalmology-IJO (English edition) is a global ophthalmological scientific publication and a peer-reviewed open access periodical (ISSN 2222-3959 print, ISSN 2227-4898 online). This journal is sponsored by Chinese Medical Association Xi’an Branch and obtains guidance and support from WHO and ICO (International Council of Ophthalmology). It has been indexed in SCIE, PubMed, PubMed-Central, Chemical Abstracts, Scopus, EMBASE , and DOAJ. IJO JCR IF in 2017 is 1.166. IJO was established in 2008, with editorial office in Xi’an, China. It is a monthly publication. General Scientific Advisors include Prof. Hugh Taylor (President of ICO); Prof.Bruce Spivey (Immediate Past President of ICO); Prof.Mark Tso (Ex-Vice President of ICO) and Prof.Daiming Fan (Academician and Vice President, Chinese Academy of Engineering. International Scientific Advisors include Prof. Serge Resnikoff (WHO Senior Speciatist for Prevention of blindness), Prof. Chi-Chao Chan (National Eye Institute, USA) and Prof. Richard L Abbott (Ex-President of AAO/PAAO) et al. Honorary Editors-in-Chief: Prof. Li-Xin Xie(Academician of Chinese Academy of Engineering/Honorary President of Chinese Ophthalmological Society); Prof. Dennis Lam (President of APAO) and Prof. Xiao-Xin Li (Ex-President of Chinese Ophthalmological Society). Chief Editor: Prof. Xiu-Wen Hu (President of IJO Press). Editors-in-Chief: Prof. Yan-Nian Hui (Ex-Director, Eye Institute of Chinese PLA) and Prof. George Chiou (Founding chief editor of Journal of Ocular Pharmacology & Therapeutics). Associate Editors-in-Chief include: Prof. Ning-Li Wang (President Elect of APAO); Prof. Ke Yao (President of Chinese Ophthalmological Society) ; Prof.William Smiddy (Bascom Palmer Eye instituteUSA) ; Prof.Joel Schuman (President of Association of University Professors of Ophthalmology,USA); Prof.Yizhi Liu (Vice President of Chinese Ophtlalmology Society); Prof.Yu-Sheng Wang (Director of Eye Institute of Chinese PLA); Prof.Ling-Yun Cheng (Director of Ocular Pharmacology, Shiley Eye Center, USA). IJO accepts contributions in English from all over the world. It includes mainly original articles and review articles, both basic and clinical papers. Instruction is Welcome Contribution is Welcome Citation is Welcome Cooperation organization International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.
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