The identification of signature genes and their relationship with immune cell infiltration in age-related macular degeneration
作者全名：Chen, Jinquan; Zhao, Long; Zhang, Longbin; Luo, Yiling; Jiang, Yuling; Peng, H.
作者地址：[Chen, Jinquan; Zhang, Longbin; Luo, Yiling; Jiang, Yuling] Tongnan Dist Peoples Hosp, Dept Ophthalmol, Chongqing, Peoples R China; [Zhao, Long; Peng, H.] Chongqing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Chongqing, Peoples R China
通信作者：Peng, H (通讯作者)，Chongqing Med Univ, Dept Ophthalmol, Affiliated Hosp 1, Chongqing, Peoples R China.
来源：MOLECULAR BIOLOGY REPORTS
ESI学科分类：MOLECULAR BIOLOGY & GENETICS
WOS号：WOS:001172270700017
JCR分区：Q3
影响因子：2.6
年份：2024
卷号：51
期号：1
开始页：
结束页：
文献类型：Article
关键词：AMD; WGCNA; Immune cells; Machine learning
摘要：BackgroundAge-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory.MethodWe obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RT-PCR were used to explore the expression of hub genes in AMD mice.ResultsWe screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-beta 2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-beta 2 mRNA and protein in the retinas of AMD mice.ConclusionWe found that four hub genes, namely, FAP, TGF-beta 2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.
基金机构：National Natural Science Foundation of China
基金资助正文：The writers extend their appreciation to the GEO repository for granting unrestricted access to the information, along with the reviewers for their valuable and insightful input.
