Bioinformatics analysis of signature genes related to cell death in keratoconus

Abstract

AbstractKeratoconus is corneal disease in which the progression of conical dilation of cornea leads to reduced visual acuity and even corneal perforation. However, the etiology mechanism of keratoconus is still unclear. This study aims to identify the signature genes related to cell death in keratoconus and examine the function of these genes. A dataset of keratoconus from the GEO database was analysed to identify the differentially expressed genes (DEGs). A total of 3558 DEGs were screened from GSE151631. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that they mainly involved in response to hypoxia, cell–cell adhesion, and IL-17 signaling pathway. Then, the cell death-related genes datasets were intersected with the above 3558 DEGs to obtain 70 ferroptosis-related DEGs (FDEGs), 32 autophagy-related DEGs (ADEGs), six pyroptosis-related DEGs (PDEGs), four disulfidptosis-related DEGs (DDEGs), and one cuproptosis-related DEGs (CDEGs). After using Least absolute shrinkage and selection operator (LASSO), Random Forest analysis, and receiver operating characteristic (ROC) curve analysis, one ferroptosis-related gene (TNFAIP3) and five autophagy-related genes (CDKN1A, HSPA5, MAPK8IP1, PPP1R15A, and VEGFA) were screened out. The expressions of the above six genes were significantly decreased in keratoconus and the area under the curve (AUC) values of these genes was 0.944, 0.893, 0.797, 0.726, 0.882 and 0.779 respectively. GSEA analysis showed that the above six genes mainly play an important role in allograft rejection, asthma, and circadian rhythm etc. In conclusion, the results of this study suggested that focusing on these genes and autoimmune diseases will be a beneficial perspective for the keratoconus etiology research.