Revealing the Roles of Pyroptosis Genes in Immune Infiltration for Intervertebral Disc Degeneration

Abstract

Abstract Background The reduction of the nucleus pulposus is a significant contributing factor to intervertebral disc degeneration (IDD), with pyroptosis being a prominent cause. However, further investigation is required to better understand the mechanisms of pyroptosis in IDD. This study aimed to identify the hub genes involved associated with pyroptosis in IDD. Methods The expression matrices of two IDD datasets were obtained from the Gene Expression Omnibus dataset. Subsequently, differentially expressed gene (DEG) analyses were performed on both datasets to identify pyroptosis-related DEGs (PRDEGs). PRDEGs underwent correlation analysis, chromosomal location and functional similarity analysis, and a series of bioinformatics methods to identify hub genes. Finally, networks comprising long non-coding ribonucleic acid (lncRNA), microRNA (miRNA), and hub genes were constructed using the Encyclopaedia of RNA Interactomes and LncBase databases. Results Following the intersection of DEGs and pyroptosis-related genes, 18 PRDEGs were identified. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analyses revealed that PRDEGs were primarily associated with the response to lipopolysaccharide and nucleotide-binding and oligomerisation domain (NOD)-like receptor (NLR) signalling pathways. Seven PRDEGs, namely NOD2, NLR family caspase activation and recruitment domain (CARD) containing 4, caspase 5, absent in melanoma 2, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a CARD, and tumour necrosis factor, were identified as hub genes. The association of IDD with resting memory CD4+ T cells was confirmed through CIBERSORT. Finally, a competing endogenous RNA network involving the seven PRDEGs was constructed. Conclusion Pyroptosis in IDD was associated with two pathways and seven hub genes. Additionally, four lncRNAs played a crucial role in the pathogenesis and progression of IDD. These potential pyroptosis-related biomarkers might offer novel approaches for further exploration into the underlying mechanisms of IDD.