Role of hypoxia-related differentially expressed genes in pathogenesis of keratoconus and construction of diagnostic models.

Keratoconus is a dilated corneal disorder caused by multiple factors, which is characterized by progressive thinning and protrusion of the paracentral cornea. It may be influenced both by genetic and environmental factors. Clinically, it manifests as significant irregular astigmatism in the affected eye, which can result in irreversible vision impairment that is challenging to correct with standard spectacles. Nevertheless, the specific hypoxia-related genes implicated in keratoconus, along with their diagnostic significance, remain inadequately explored. This research intend to explore the involvement of hypoxia-related differentially expressed genes in the pathogenesis of keratoconus, aiming to explore new diagnostic methods and therapeutic strategies. By employing bioinformatics methodologies, we analyzed RNA sequencing and microarray data from the GEO database to pinpoint differentially expressed genes associated with hypoxic conditions in keratoconus. Our analysis identified 490 differentially expressed genes, encompassing 62 genes that were upregulated and 428 that were downregulated, indicating their probable role in the advancement of keratoconus. Gene Ontology and pathway enrichment analyses showed that 43 HRDEGs were significantly enriched in various biological processes, underscoring the pivotal influence of hypoxia in the pathophysiology of keratoconus. Additionally, a support vector machine model highlighted nine hypoxia-related differentially expressed genes, while least absolute shrinkage and selection operator regression identified five genes suitable for modeling, culminating in two diagnostic models exhibiting high accuracy (AUC >0.9) for the early detection of keratoconus. Furthermore, the immune cell infiltration analysis revealed a positive association between DUSP1 and follicular helper T cells, as well as a negative association with resting mast cells, indicating an immune-related aspect in the progression of keratoconus. The results of our study lay the groundwork for subsequent investigations into the molecular pathways involved in keratoconus, as well as the creation of specialized diagnostic instruments.