Development and Validation of a Ferroptosis-Related Gene Signature for Intervertebral Disc Degeneration

Abstract

Background As a natural process of aging, intervertebral disc degeneration is more prone to degeneration, with limited repair ability, which is closely related to ageing and excessive manual labor. The main manifestations include the formation of fissures in the annulus fibrosus, the reduction of water in the intervertebral disc, and the decrease of elasticity. However, the molecular mechanism of intervertebral disc degeneration is still unclear. Methods In this study, key biomarkers in intervertebral disc degeneration were identified through bioinformatics. GSE70362 and GSE56081 were downloaded from the GEO database, and then the two datasets were differentially analyzed and validated for their expression, immune infiltration analysis, functional enrichment analysis, and potential drug prediction through the Connectivity Map (CMap) database. Results A total of 352 and 9815 differential genes were identified by GSE70362, GSE56081, respectively. The up-regulated and down-regulated genes of the two datasets were intersected with ferroptosis genes to obtain five key genes that were significantly correlated with immune cell content, namely AKR1C3, CKB, KRT19, MT1G and MUC1. The ROC results showed that the five core genes could well predict the occurrence and development of the disease. In addition, the results of CMap suggested that four drugs, including 1-Phenylbiguanide, LY-2183240, Flubendazole and Penciclovir, have the potential to reverse intervertebral disc degeneration. Conclusion Exploring the expression levels of five key genes in intervertebral disc degeneration is conductive to providing new ideas for the prevention and treatment of intervertebral disc degeneration. Moreover, Flubendazole and Penciclovir have the potential to provide options for clinical treatment of intervertebral disc degeneration.