Unveiling immune mechanisms and potential biomarkers in intervertebral disc degeneration through integrated analysis.

Abstract

Immune regulation plays an important role in the pathogenesis of intervertebral disc degeneration (IDD). However, the mechanism of immune regulation in IDD is still unclear. All IDD data were downloaded from a public database. The differentially expressed (DE) immune-related genes in IDD were identified by the limma package in R. Functional enrichment analyses were performed to explore potential immune-related biological pathways in IDD. We also identified differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and constructed an mRNA-miRNA-lncRNA network. ROC analysis was performed to reveal potential diagnostic biomarkers for IDD. To understand the potential role of immune cells in IDD, xCell and Pearson correlation analyses were performed. Finally, expression validation was performed using real-time PCR. C5AR2, NFATC2, FCGR3A, hsa-miR-302d-3p, and MIR17HG were identified in IDD. ROC analysis results suggested that C5AR2 had good diagnostic accuracy, and FCGR3A and NFATC2 had sufficient diagnostic accuracy, which implied that they may be potential diagnostic markers of IDD. We also found that a large number of immune-related signaling pathways, such as cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, and Nod-like receptor signaling pathway, were significantly enriched. C5AR2, hsa-miR-302d-3p, and MIR17HG were significantly correlated with multiple immune cell types, such as cDC, CD8+ Tem, macrophage M1, neutrophils, and plasma cells. The C5AR2-hsa-miR-302d-3p-MIR17HG axis may play a role in immune regulation by regulating the infiltration level of related immune cells in the IDD microenvironment. The identification of key immune-related molecules, cells, and signaling pathways in IDD is of great significance to reveal the pathogenesis of IDD.