Identification of differentially expressed and methylated genes and construction of a co-expression network in age-related macular degeneration

被引：9
作者：
Liang, Gaohua [1 ,2 ]
Ma, Wenhao [2 ]
Luo, Yanni [2 ]
Yin, Jiayang [1 ]
Hao, Lili [1 ]
Zhong, Jingxiang [1 ,3 ]
机构：
[1] Jinan Univ, Affiliated Hosp 1, Dept Ophthalmol, 613 West Huangpu Ave, Guangzhou 510632, Peoples R China
[2] Youjiang Med Univ Nationalities, Affiliated Hosp, Dept Ophthalmol, Baise, Peoples R China
[3] Jinan Univ, Ophthalmol Inst, 601 West Huangpu Ave, Guangzhou 510630, Peoples R China
来源：
ANNALS OF TRANSLATIONAL MEDICINE | 2022年 / 10卷 / 04期
关键词：
Age-related macular degeneration (AMD); methylation; weighted gene co-expression network analysis (WGCNA); pathway; co-expression module;
D O I：
10.21037/atm-21-7043
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Background: Age-related macular degeneration (AMD) is the leading cause of blindness for people over 50 years old worldwide. The purpose of this study was to identify differentially expressed and methylated genes (DEMGs) and construct a co-expression network for AMD. Methods: Microarray expression (GSE29801 dataset) and DNA methylation (GSE102952 dataset) profiles were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were analyzed between AMD retina tissues and normal retina tissues. A protein-protein interaction (PPI) network was constructed and hub genes were screened, followed by functional enrichment analysis. Then, weighted gene co-expression network analysis (WGCNA) was conducted. The ARPE-19 cells were maintained in a hypoxic state to construct an AMD cellular model. Enzyme-linked immunosorbent assay (ELISA) and the real-time qPCR (RT-qPCR) were performed for validation. Results: After overlapping, 16 hypermethylated and down-regulated genes and 15 hypomethylated and up regulated genes were identified for extramacular AMD. A total of 4 hub genes (LMNB2, EMD, HLA-A, and HLA-B) were screened for AMD in the extramacular retina. Furthermore, 13 hypermethylated and down regulated genes and 31 hypomethylated and up-regulated genes were identified for macular AMD. Among them, 11 hub genes (HLA-A, HLA-B, HLA-DRB1, IFITM3, SAT1, MAOB, CHRDL1, FSTL1, HSPA1A, AR, and YAP1) were considered hub genes. The DEMGs were distinctly related with immune-related biological processes and pathways. A total of 16 co-expression modules were constructed, of which 2 significantly correlated with AMD. The genes in the 2 modules were involved in various crucial signaling pathways. The HIF1 alpha and VEGF levels were significantly up-regulated in cell supernatant of hypoxia-induced ARPE-19 cells, indicating that the AMD cellular model was successfully established. Hub genes including CHRDL, FSTL1, and IFITM3 displayed significantly higher expression in hypoxia-induced ARPE-19 cells compared to normal cells. Greater up-regulation of CHRDL, FSTL1, and IFITM3 expression was found in hypoxiainduced ARPE-19 cells than in normal cells. Conclusions: These findings offered several key DEMGs and pathways for AMD and constructed AMDrelated co-expression modules, deepening understanding of the pathogenesis of AMD.
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页数：19
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