ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1583237
Identification and validation of integrated stress response related genes as biomarkers for age-related macular degeneration
Provisionally accepted
- 1Shenzhen Baoan People's Hospital, Shenzhen, China
- 2Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China
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Background: Age-related macular degeneration (AMD) is a prevalent ocular condition associated with aging, serving as a significant contributor to vision loss among middle-aged and older individuals. Studies have shown that AMD and integrated stress response (ISR) are associated with oxidative stress, but no specific molecular mechanisms have been identified. Therefore, this study aimed to identify potential biomarkers for AMD through bioinformatics analysis based on the transcriptome database and integrated stress response related genes (ISR-RGs).In this study, transcriptomics data GSE76237, GSE247168 and ISR-RGs were sourced from public databases and related literature. The biomarkers associated with AMD, were identified by differentially expressed genes (DEGs) analysis, intersection of common DEGs and ISR-RGs, mechine algorithm. After that, nomograms, GSEA and immune infiltration analysis were performed for the biomarkers. Then, the effects of transcription factors (TFs) and miRNAs on biomarkers were explored by constructing a TF-biomarker-miRNA regulatory network. In addition, potential effective drugs of the biomarkers were explored by constructing a biomarker-effective drug interaction network. Finally, we verified the gene expression of the biomarkers by RT-qPCR.We obtained 2,567 and 1,454 DEGs in GSE76237 and GSE247168, respectively. The upand down-regulated genes shared in both datasets were intersected with ISR-RGs taken to obtain 8 candidate genes. SLFN11 and GRIN1 were identified as common biomarkers for AMD. An analysis of the nomogram model of biomarkers revealed good diagnostic predictive abilities (AUC > 0.7). SLFN11 and GRIN1 were mainly enriched in pathways such as proteasome, lysosome, neuroactive ligand receptor interaction. In addition, the disease group's monocyte expression was significantly higher than the control group's in GSE76237 (p<0.01). 13 relevant miRNAs and 27 TFs were obtained by prediction, with three shared TFs. 17 potentially effective drugs were predicted. RT-qPCR validation showed in AMD patients, SLFN11 and GRIN1 expression was significantly higher compared to controls (p < 0.05). Only SLFN11 expression was consistent with the bioinformatics analysis.Conclusion: SLFN11 and GRIN1 have been identified as AMD biomarkers, exhibiting robust diagnostic performance, and providing new insight into the condition.
Keywords: age-related macular degeneration, biomarkers, integrated stress response, SLFN11, Grin1
Received: 25 Feb 2025; Accepted: 26 Jun 2025.
Copyright: © 2025 Niu, Jin, Hu, Wang, Hao, Geng and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jingyi Niu, Shenzhen Baoan People's Hospital, Shenzhen, China
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