AUTHOR=Yu Fenfen , Wang Congyao , Su Yihua , Chen Tingting , Zhu Wenhui , Dong Xia , Ke Wanyi , Cai Leqi , Yang Shasha , Wan Pengxia 

TITLE=Comprehensive analysis of ferritinophagy-related genes and immune infiltration landscape in diabetic retinopathy

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1177488

DOI=10.3389/fendo.2023.1177488

ISSN=1664-2392

ABSTRACT=Background: Diabetic retinopathy (DR) is deemed a microangiopathy and neurodegenerative disorder, which is a primary reason of visual impairment in the world. Ferritinophagy is a critical regulator of ferroptosis and has a vital part in the etiopathogenesis of DR. Nevertheless, its molecular mechanism in DR remains to be expounded. Methods: GSE146615 dataset was adopted to identify ferritinophagy-related differentially expressed genes (FRDEGs). The interactions and biological functions of the genes were described by means of functional enrichment analysis (FEA). The enriched gene sets were analyzed utilizing Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). Then, identification of hub genes was performed utilizing protein-protein interaction (PPI) analysis. mRNA-miRNA, mRNA-transcription factors (TF), mRNA-drugs, mRNA-RNA binding proteins (RBP) interaction networks were constructed. In addition, datasets GSE60436 and GSE94019were utilized for validation. The diagnostic performance of FRDEGs was assessed by means of receiver-operating characteristic curve monofactor analysis, followed by immune infiltration analysis. Lastly, quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to analyze validation of genes.In total, identification of 8 FRDEGs was completed utilizing differential expression analysis. FEA mainly implicated the autophagy of mitochondrion, mitochondrion disassembly, autophagosome assembly and organization pathways. GSEA and GSVA analysis mainly implicated the interferon alpha response, ultraviolet response up, interferon gamma response, apical junction, pical surface, and allograft rejection pathways. BECN1 and HERC2 displayed high diagnostic accuracies in validation sets. Immune infiltration analysis revealed that several immune cells related to ferritinophagy may be play potential roles in DR. Finally, qRT-PCR was utilized for validating the upregulated expression of BECN1 as well as downregulated expression of BCAT2 and ATG7 in DR model.: BECN1, HERC2, ATG7 and BCAT2 act as the potential biomarkers for DR and might regulate ferritinophagy and the immune microenvironment to influence the development and progression. This research can provide new insights into pathogenesis of DR related to ferritinophagy.