Significance of oxidative stress in the diagnosis and subtype classification of intervertebral disc degeneration

Abstract

Abstract Intervertebral disc degeneration (IVDD) is a common disease of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance of extracellular matrix synthesis and catabolism, and an inflammatory response. Although great efforts have been made in the study of IVDD, the specific pathogenesis and the associated regulatory genes are still not fully understood to date. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or increases the production of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 oxidative stress-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408, and subjected these DEGs to GO and KEGG analysis. Then, based on these 35 differentially expressed genes, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1), and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to predict the risk of IVDD patients, we developed a nomogram model. Based on the six previously screened hub genes, we obtained two OSRG clusters (cluster A and B) by consensus clustering. Then, 3147 DEGs were obtained by differential gene expression analysis of all samples in the two clusters, and based on this, all samples were further divided into two gene clusters (A and B). We obtained the OSRG scores for every sample using the PCA algorithm and measured the differences among the different clusters. We investigated differences in immune cell infiltration levels between different clusters and discovered that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. To summarize, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.