Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization
Abstract Glaucoma poses a significant global health challenge, yet reliable biomarkers for its diagnosis and treatment remain scarce. This study employed Mendelian randomization (MR) and bioinformatics approaches to identify potential biomarkers for glaucoma. Using the GSE9944 dataset, differentiall...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-03781-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849402832492429312 |
|---|---|
| author | Xiuli Lin Chuanyong Ma Xiaoxue Zhang Yuzhe Qiu Yi Cui Nuo Xu |
| author_facet | Xiuli Lin Chuanyong Ma Xiaoxue Zhang Yuzhe Qiu Yi Cui Nuo Xu |
| author_sort | Xiuli Lin |
| collection | DOAJ |
| description | Abstract Glaucoma poses a significant global health challenge, yet reliable biomarkers for its diagnosis and treatment remain scarce. This study employed Mendelian randomization (MR) and bioinformatics approaches to identify potential biomarkers for glaucoma. Using the GSE9944 dataset, differentially expressed genes (DEGs) were identified and analyzed through protein-protein interaction (PPI) networks and functional enrichment. MR analysis selected DEGs for further evaluation using support vector machine-recursive feature elimination (SVM-RFE), with genes exhibiting high differential expression and an area under the curve (AUC) > 0.7 considered as candidate biomarkers. Among 836 DEGs, the PPI network revealed complex interactions, and functional enrichment highlighted significant involvement of the PI3K-AKT and MAPK signaling pathways. MR analysis linked 113 DEGs to glaucoma, with 57 genes showing consistent expression trends. SVM-RFE identified six signature genes, among which ATP6V0D1 and FAM89B emerged as robust biomarkers (AUC > 0.7). Molecular regulatory network analysis and drug prediction analysis further revealed potential mechanisms and compounds targeting these biomarkers, providing new therapeutic avenues for glaucoma. Experimental validation confirmed that ATP6V0D1 and FAM89B were significantly downregulated under both mechanical and swelling stress conditions, with concurrent suppression of the PI3K/AKT pathway. In conclusion, ATP6V0D1 and FAM89B are promising biomarkers for glaucoma, offering potential applications in diagnosis, treatment, and advancing the understanding of glaucoma pathogenesis. |
| format | Article |
| id | doaj-art-dce7e45564a1464d9d3768aca2f6cc29 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dce7e45564a1464d9d3768aca2f6cc292025-08-20T03:37:27ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-03781-3Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomizationXiuli Lin0Chuanyong Ma1Xiaoxue Zhang2Yuzhe Qiu3Yi Cui4Nuo Xu5Department of Ophthalmology, Fujian Geriatric Hospital, North Hospital of Fujian Provincial HospitalDepartment of Ophthalmology, Fujian Geriatric Hospital, North Hospital of Fujian Provincial HospitalDepartment of Ophthalmology, Fujian Geriatric Hospital, North Hospital of Fujian Provincial HospitalDepartment of Ophthalmology, Fujian Geriatric Hospital, North Hospital of Fujian Provincial HospitalDepartment of Ophthalmology, Fujian Medical University Union HospitalDepartment of Ophthalmology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial HospitalAbstract Glaucoma poses a significant global health challenge, yet reliable biomarkers for its diagnosis and treatment remain scarce. This study employed Mendelian randomization (MR) and bioinformatics approaches to identify potential biomarkers for glaucoma. Using the GSE9944 dataset, differentially expressed genes (DEGs) were identified and analyzed through protein-protein interaction (PPI) networks and functional enrichment. MR analysis selected DEGs for further evaluation using support vector machine-recursive feature elimination (SVM-RFE), with genes exhibiting high differential expression and an area under the curve (AUC) > 0.7 considered as candidate biomarkers. Among 836 DEGs, the PPI network revealed complex interactions, and functional enrichment highlighted significant involvement of the PI3K-AKT and MAPK signaling pathways. MR analysis linked 113 DEGs to glaucoma, with 57 genes showing consistent expression trends. SVM-RFE identified six signature genes, among which ATP6V0D1 and FAM89B emerged as robust biomarkers (AUC > 0.7). Molecular regulatory network analysis and drug prediction analysis further revealed potential mechanisms and compounds targeting these biomarkers, providing new therapeutic avenues for glaucoma. Experimental validation confirmed that ATP6V0D1 and FAM89B were significantly downregulated under both mechanical and swelling stress conditions, with concurrent suppression of the PI3K/AKT pathway. In conclusion, ATP6V0D1 and FAM89B are promising biomarkers for glaucoma, offering potential applications in diagnosis, treatment, and advancing the understanding of glaucoma pathogenesis.https://doi.org/10.1038/s41598-025-03781-3GlaucomaATP6V0D1Mendelian randomizationFAM89B |
| spellingShingle | Xiuli Lin Chuanyong Ma Xiaoxue Zhang Yuzhe Qiu Yi Cui Nuo Xu Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization Scientific Reports Glaucoma ATP6V0D1 Mendelian randomization FAM89B |
| title | Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization |
| title_full | Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization |
| title_fullStr | Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization |
| title_full_unstemmed | Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization |
| title_short | Identifying diagnostic biomarkers for glaucoma based on transcriptome combined with Mendelian randomization |
| title_sort | identifying diagnostic biomarkers for glaucoma based on transcriptome combined with mendelian randomization |
| topic | Glaucoma ATP6V0D1 Mendelian randomization FAM89B |
| url | https://doi.org/10.1038/s41598-025-03781-3 |
| work_keys_str_mv | AT xiulilin identifyingdiagnosticbiomarkersforglaucomabasedontranscriptomecombinedwithmendelianrandomization AT chuanyongma identifyingdiagnosticbiomarkersforglaucomabasedontranscriptomecombinedwithmendelianrandomization AT xiaoxuezhang identifyingdiagnosticbiomarkersforglaucomabasedontranscriptomecombinedwithmendelianrandomization AT yuzheqiu identifyingdiagnosticbiomarkersforglaucomabasedontranscriptomecombinedwithmendelianrandomization AT yicui identifyingdiagnosticbiomarkersforglaucomabasedontranscriptomecombinedwithmendelianrandomization AT nuoxu identifyingdiagnosticbiomarkersforglaucomabasedontranscriptomecombinedwithmendelianrandomization |