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Published on: March 10, 2023
Cuproptosis-related signature and immune infiltration in age-related macular degeneration
Chen Li1, Yi-Cheng Lu1, Ming-Xuan Chen2
1Department of Ophthalmology, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China.
Aim:
To investigate cuproptosis-related molecular and immune infiltration in age-related macular degeneration (AMD) development and establish a predictive model.
Methods:
The expression profiles of cuproptosis-related genes and immune signature in AMD based on the microarray dataset GSE29801 were analyzed. A total of 142 AMD samples were used to identify the cuproptosis-related differentially expressed genes (Cu-DEGs), together with the immune cell infiltration. To further refine the list of potential genes for AMD diagnosis, three machine learning techniques were used, and an external dataset were applied for confirming the accuracy of the predictive performance. Reverse transcription polymerase chain reaction (RT-PCR) were also performed to examine the level of mRNA of hub genes. The activated immune responses and Cu-DEGs were assessed between AMD and controls.
Results:
Six genes, including ATP7A, DBT, VEGFA, UBE2D3, CP, SLC31A1, were screened as cuproptosis-signature in AMD via three machine learning methods. Next, SLC31A1 and VEGFA was selected as hub genes by performance evaluation in an external dataset GSE160011, further analysis showed that SLC31A1 and VEGFA were associated with pathways related to immune signaling and immune function, which were then observed in relation to infiltrating immune cells. Finally, the mRNA expression levels of SLC31A1 and VEGFA were significantly higher in laser induced choroidal neovascularization (CNV) group than in control group detected by RT-PCR.
Conclusion:
In this study, the possible relationship between cuproptosis and AMD is expounded systematically. A predictive model is developed to assess the risk of cuproptosis-related genes and their clinical prognostic value in AMD patients.
Insights
This study explores cuproptosis-related genes and immune infiltration in age-related macular degeneration (AMD). A predictive model using hub genes SLC31A1 and VEGFA was developed for AMD risk assessment.
Area of Science:
- Ophthalmology
- Molecular Biology
- Immunology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- Cuproptosis, a newly identified cell death pathway, is implicated in various diseases.
- The role of cuproptosis in AMD pathogenesis remains unclear.
Purpose of the Study:
- To investigate cuproptosis-related molecular mechanisms and immune infiltration in AMD.
- To establish a predictive model for AMD risk based on cuproptosis-related genes.
- To explore the clinical prognostic value of these genes in AMD.
Main Methods:
- Analysis of microarray datasets (GSE29801, GSE160011) for cuproptosis-related differentially expressed genes (Cu-DEGs) and immune cell infiltration in AMD.
- Application of three machine learning techniques to identify diagnostic genes.
- Validation using an external dataset and reverse transcription polymerase chain reaction (RT-PCR) for hub gene expression.
Main Results:
- Six cuproptosis-signature genes were identified in AMD.
- SLC31A1 and VEGFA were selected as hub genes, associated with immune signaling pathways.
- Higher mRNA expression of SLC31A1 and VEGFA was observed in laser-induced choroidal neovascularization (CNV) models.
Conclusions:
- Cuproptosis is systematically linked to AMD development.
- A predictive model incorporating cuproptosis-related genes (SLC31A1, VEGFA) offers prognostic value for AMD patients.
- These findings highlight potential therapeutic targets for AMD.
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