Novel Biomarkers Related to Oxidative Stress and Immune Infiltration in Intervertebral Disc Degeneration

The complexity of the pathogenesis of intervertebral disc degeneration (IVDD)-a degenerative disease commonly seen in the elderly-has yet to be elucidated. However, in recent years, it has been discovered that immune cells infiltrate the nucleus pulposus (NP) of IVDD. Few scholars have given heed to the intricate interaction between persistent inflammation and oxidative stress (OS) in connection with the pathogenesis of IVDD. We aimed to recognize biomarkers of immune infiltration and OS in IVDD in order to further reveal the complex pathogenesis of IVDD. 1799 differentially expressed genes were identified by GSE70362 dataset of GEO database. 43 differentially expressed genes were identified after intersection with OS-related genes. The R language packages of CIBERSORT, MCPcounter and WGCNA were subsequently used to compare the differences in immune infiltration levels between IVDD and control samples. The differentially expressed genes related to OS and the immune-related module genes of WGCNA were intercrossed again to obtain 10 differentially expressed key genes related to both immune and OS. To identify these genes, a protein-protein interaction (PPI) network was created using STRING database and Cytoscape software, and five core key genes were initially identified. Subsequently, four diagnostic markers PPIA, MAP3K5, PXN and JAK2 were identified using the GSE122429 external dataset for validation. In a cellular model of OS in NP cells, we finally identified the up-regulation of PPIA and PXN genes, which could be used as novel markers for IVDD.