Development of a Novel Inflammatory-Associated Gene Signature and Immune Infiltration Patterns in Intervertebral Disc Degeneration

Abstract

Background. Both inflammatory factors and immune response play important roles in the pathogenesis of intervertebral disc degeneration (IDD). However, a comprehensive analysis of interaction between inflammatory response-associated genes (IRGs) and immune microenvironment in patients with IDD remains lacking. Hence, the current research is aimed at investigating the correlations between IRG signatures and immune cells in the progression of IDD. Methods. The expression profiles (GSE27494 and GSE41883) and IRGs were downloaded from the Gene Expression Omnibus (GEO) database and Molecular Signature Database (MSigDB), respectively. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were used to identify the pivotal modules and common differentially expressed genes (DEGs) associated with IDD. Subsequently, we retrieved differentially expressed IRGs (DE-IRGs) by intersecting IRGs and DEGs for enrichment analysis. Next, LASSO regression analyses were performed to screen optimal marker genes for IDD prediction. Additionally, we validated differences DE-IRGs between IDD patients and controls in GSE150408. Finally, the infiltration alteration of immune cells was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. Results. A total of 10 upregulated differentially expressed inflammatory genes were identified that were obviously related to progression of IDD. Functional analysis results revealed that DE-IRGs were mainly enriched in signaling pathways TNF, IL-17, NOD-like receptor, and NF-kappa B pathway. A five-gene signature that consisted of IL-1β, LIF, LYN, NAMPT, and SLC7A2 was constructed by the LASSO Cox regression. IL1B, LYN, and NAMPT were further validated as optimal candidate genes in the pathophysiology of IDD. In addition, there was a remarkable immune cell infiltration difference between the healthy and IDD groups. The proportions for dendritic cells activated, mast cells activated, and neutrophils in the IDD group were significantly higher than those in the normal group, while the proportion of some cells was lower than that of the normal group, such as T cell CD4 memory resting, NK cells activated, and macrophage M0. Furthermore, correlation analysis indicated IL-1β, LYN, and NAMPT were closely implicated with immune cell infiltration in IDD development. Conclusions. We explored an association between inflammatory response-associated signature and immune infiltration in IDD and validated that IL-1β, LYN, and NAMPT might serve as biomarkers and therapeutic targets for IDD in the future.

Identifification and validation of ferroptosis signatures and immune infifiltration characteristics associated with intervertebral disc degeneration

“…The findings demonstrated that whereas eosinophils and Th2 cells reduced in the deteriorated nucleus pulposus compared to the normal group, the number of macrophages, CD8T cells, dendritic cells, and Th17 cells rose. The importance of macrophage infiltration in the etiology of IDD has been validated by recent research (Lan et al, 2022;Yan et al, 2022).…”

Comprehensive analysis of gene expression profiles of annulus fibrosus subtypes and hub genes in intervertebral disc degeneration

“…Zhang et al identified inflammatory response-related features using WGCNA and LASSO, and explored the relationships between them and immune infiltration in IVDD. In addition, IL-1β, LYN, and NAMPT were validated as possible biomarkers [ 28 ]. Zhu et al constructed good genetic and lncRNA diagnostic models by systematic analysis of lncRNA and microRNA expression profiles and lncRNA and miRNA expression between IVDD and healthy patients [ 29 ].…”

Identification and validation of ferroptosis-related gene signature in intervertebral disc degeneration

“…Accumulating studies have attempted to explore the underlying mechanisms of IDD by bioinformatic analysis, including inflammatory response, immune infiltration, mitochondrial dysfunction, etc ( 53 , 54 ). The present study focused on the association between ferroptosis with IDD, and provided novel insights into the pathogenesis of IDD.…”