Identification of Key Modules and Hub Genes of Annulus Fibrosus in Intervertebral Disc Degeneration

Abstract

Background: Intervertebral disc degeneration impairs the quality of patients lives. Even though there has been development of many therapeutic strategies, most of them remain unsatisfactory due to the limited understanding of the mechanisms that underlie the intervertebral disc degeneration.Questions/purposes: This study is meant to identify the key modules and hub genes related to the annulus fibrosus in intervertebral disc degeneration (IDD) through: (1) constructing a weighted gene co-expression network; (2) identifying key modules and hub genes; (3) verifying the relationships of key modules and hub genes with IDD; and (4) confirming the expression pattern of hub genes in clinical samples.Methods: The Gene Expression Omnibus provided 24 sets of annulus fibrosus microarray data. Differentially expressed genes between the annulus fibrosus of degenerative and non-degenerative intervertebral disc samples have gone through the Gene Ontology (GO) and pathway analysis. The construction of a gene network and classification of genes into different modules were conducted through performing Weighted Gene Co-expression Network Analysis. The identification of modules and hub genes that were most related to intervertebral disc degeneration was proceeded. In order to verify the relationships of the module and hub genes with intervertebral disc degeneration, Ingenuity Pathway Analysis was operated. Clinical samples were adopted to help verify the hub gene expression profile.Results: One thousand one hundred ninety differentially expressed genes were identified. Terms and pathways associated with intervertebral disc degeneration were presented by GO and pathway analysis. The construction of a Weighted Gene Coexpression Network was completed and clustering differentially expressed genes into four modules was also achieved. The module with the lowest P-value and the highest absolute correlation coefficient was selected and its relationship with intervertebral disc degeneration was confirmed by Ingenuity Pathway Analysis. The identification of hub genes and the confirmation of their expression profile were also realized.Conclusions: This study generated a comprehensive overview of the gene networks underlying annulus fibrosus in intervertebral disc degeneration.Clinical Relevance: Modules and hub genes identified in this study are highly associated with intervertebral disc degeneration, and may serve as potential therapeutic targets for intervertebral disc degeneration.

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

“…Current treatment of IDD, including conservative therapies and surgical interventions, often only alleviates the patients’ pain without preventing the progression of IDD ( Stich et al, 2020 ). Furthermore, the clinical results are suboptimal ( Wang H. et al, 2020 ). Surgical therapies are generally associated with various complications ( Smolders et al, 2013 ).…”

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

“…Chen et al used an integrated bioinformatics approach to generate a comprehensive overview of the gene networks associated with the AF in IVDD. This identified DSE, IL17RD, DUSP18, ROBO3, BANK1, MRC2, LGALSL, TFPI, GAP43, and HYAL1 as hub genes [ 33 ]. By constructing a PPI network, Li et al found that the MMP2 and AGE-RAGE signaling pathways as well as the estrogen signaling pathway may play important roles in the onset and development of IVDD [ 34 ].…”

“…LGALSL, TFPI, GAP43, and HYAL1 as hub genes [33]. By constructing a PPI network, Li et al found that the MMP2 and AGE-RAGE signaling pathways as well as the estrogen signaling pathway may play important roles in the onset and development of IVDD [34].…”

Identification of Cervical Disc Degeneration and Genes Associated with Immune Infiltration

“…Studies have shown that the density of blood vessels and nerves is positively correlated with the degree of disc degeneration [9] . Whole-genome analysis has shown that the expression of nerve-related genes increases with the upregulation of proin ammatory cytokine and chemokine-related genes in degenerated human AF [10] . In addition, the NP, which is the largest avascular organ in the center of the disc, is uniquely isolated from the human immune system due to its anatomical structure.…”