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  4. Vol 6, Issue 4, 2025

Identification of Hypoxia-Related Biomarkers for Proliferative Diabetic Retinopathy: An Integrative Bioinformatics Analysis

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DOI: 10.23977/medsc.2025.060417 | Downloads: 0 | Views: 128

Author(s)

Dingqiao Wang 1, Peidong Yuan 2, Hongzhi Yuan 2

Affiliation(s)

1 Department of Ophthalmology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
2 Department of Ophthalmology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China

Corresponding Author

Hongzhi Yuan

ABSTRACT

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes, in which hypoxia plays a central pathogenic role. However, the hypoxia-associated molecular mechanisms and biomarkers in PDR remain incompletely understood. RNA sequencing data from patients with PDR and healthy controls (GSE146615) were analyzed to identify differentially expressed genes (DEGs). Hypoxia-related genes (HRGs) were obtained from the GeneCards database and integrated with DEGs and weighted gene co-expression network analysis (WGCNA) modules. Candidate genes were refined using least absolute shrinkage and selection operator (LASSO) regression and extreme gradient boosting (XGBoost). Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis. Immune infiltration was estimated with the CIBERSORT algorithm, and biomarker–immune cell correlations were examined. We identified 1,650 DEGs in PDR, enriched in immune regulation, vascular function, and mitochondrial pathways. Intersection analysis identified 13 hypoxia-related genes, of which four—CXCL9, DSC2, DSC3, and PITRM1—were selected as key biomarkers by LASSO and XGBoost. ROC analysis showed strong diagnostic performance for PITRM1 (AUC = 0.863), DSC2 (AUC = 0.861), DSC3 (AUC = 0.837), and CXCL9 (AUC = 0.749). Immune infiltration analysis revealed increased plasma cells and CD8⁺ T cells, and decreased resting mast cells in PDR. This integrative bioinformatics analysis identified four hypoxia-related genes as potential diagnostic biomarkers for PDR, providing insights into hypoxia-driven immune and vascular changes in disease pathogenesis. These findings may inform future diagnostic and therapeutic strategies.

KEYWORDS

Proliferative Diabetic Retinopathy, Hypoxia-Related Genes, CXCL9, DSC2, DSC3, PITRM1, Bioinformatics, Immune Infiltration

CITE THIS PAPER

Dingqiao Wang, Peidong Yuan, Hongzhi Yuan, Identification of Hypoxia-Related Biomarkers for Proliferative Diabetic Retinopathy: An Integrative Bioinformatics Analysis. MEDS Clinical Medicine (2025) Vol. 6: 105-118. DOI: http://dx.doi.org/10.23977/medsc.2025.060417.

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