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. 2022 Sep 22:2022:2481071.
doi: 10.1155/2022/2481071. eCollection 2022.

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

Tao Lan  1 , Zhihao Hu  1 , Weizhuang Guo  1 , Bin Yan  1 , Yuantao Zhang  2
Affiliations

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

Tao Lan et al. Oxid Med Cell Longev. .

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.

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Conflict of interest statement

The authors have no conflicts of interest to disclose in relation to this article.

Figures

Figure 1
Figure 1
Research flow chart of this study.
Figure 2
Figure 2
Identification of differentially expressed genes associated with intervertebral disc degeneration (IDD). Heatmap and volcano map of DEGs between IDD patients and healthy control in (a, b) GSE27494 and (c, d) GSE41883. Red represents upregulated genes, green or blue represents downregulated genes, and black represents no significant difference genes.
Figure 3
Figure 3
Identification of key modules that relate to IDD via WGCNA. (a, b) The cluster dendrogram of coexpression network modules and module-trait relationships in (a, b) GSE27494 and (c, d) GSE41883. Various colors represent different modules. Each row corresponds to a color module and column corresponds to a clinical trait (IDD and healthy).
Figure 4
Figure 4
Screening main inflammatory associated genes in IDD. (a) Venn diagram between WGCNA modules and DEGs. (b) The overlapped DEGs and inflammatory associated genes.
Figure 5
Figure 5
Top 10 differentially expressed inflammatory-related genes in IDD. Boxplots of the expression levels of 10 differentially expressed IRGs in IDD and healthy controls. The green box plots represent the expression in healthy controls, whereas the red box plots represent the expression in IDD.
Figure 6
Figure 6
Correlation between differentially expressed IRGs in IDD. (a) Circos plot of differentially expressed IRGs. (b) Correlation plot of differentially expressed IRGs. (c) Correlation network between IRGs. (d) Radar plot of IRGs.
Figure 7
Figure 7
GO and KEGG analyses of DE-IRGs in the pathogenesis of IDD. (a) Significantly enriched GO terms of the DE-IRGs. (b) Significantly enriched KEGG pathways of the DE-IRGs.
Figure 8
Figure 8
LASSO screen of the hub differentially expressed inflammatory-related genes. (a, b) Least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to screen candidate IRGs.
Figure 9
Figure 9
Significant gene expression boxplots of IL-1β, LYN, and NAMPT between IDD and healthy controls in GSE150408.
Figure 10
Figure 10
The immune landscape in IDD patients. (a) Bar plot showing the relative proportions of 22 immune cell populations in IDD samples. (b) Violin plot comparing immune cell compositions in the IDD patients and healthy controls. (c) Pearson's correlation analysis of different infiltrating immune cell subpopulations.
Figure 11
Figure 11
Correlation between immune cells and IL-1β, LYN, and NAMPT.
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