Hub Genes and Key Pathways of Intervertebral Disc Degeneration: Bioinformatics Analysis and Validation.
Ontology highlight
ABSTRACT: Objective
To identify significant pathways and genes in intervertebral disc degeneration (IDD) based on bioinformatics analysis.Design
The GEO database was used to download the GSE124272 dataset. Differentially expressed genes (DEGs) were analyzed using Limma package in R language. Then, gene ontologies (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein-protein interaction (PPI) networks were used to further identify hub genes. The mRNA expression levels of top six hub genes were verified.Results
We found 563 DEGs, of which 214 were upregulated and 349 were downregulated. The top 5 GO terms and pathways were shown including immune response, cell cycle, and p53 pathway. Based on the PPI analysis, we verified the mRNA expression levels of 6 hub genes. The mRNA levels of CHEK1, CDCA2, SKA3, and KIF20A were upregulated in degenerative NP tissue than in healthy NP tissue. However, the mRNA level of BUB1 and SPC25 was downregulated.Conclusions
This study may provide new biomarkers for the IDD and treatments to repair IDD related to CHEK1, CDCA2, SKA3, BUB1, KIF20A, and SPC25.
SUBMITTER: Zhang Z
PROVIDER: S-EPMC8449732 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundIntervertebral disc degeneration (IDD) is widely known as the main contributor to low back pain which has a negative socioeconomic impact worldwide. However, the underlying mechanism remains unclear. This study aims to analyze the dataset GSE23130 using bioinformatics methods to identify the pivotal genes and pathways associated with IDD.Material/methodsThe gene expression data of GSE23130 was downloaded, and differentially expressed genes (DEGs) were extracted from 8 samples and 15 controls. GO and KEGG pathway enrichment analyses were performed. Also, protein-protein interaction (PPI) network was constructed and visualized, followed by identification of hub genes and key module.ResultsA total of 30 downregulated and 79 upregulated genes were identified. The DEGs were mainly enriched in the regulation of protein catabolic process, extracellular matrix organization, collagen fibril organization, and extracellular structure organization. Meanwhile, we found that most DEGs were primarily enriched in the PI3K-Akt signaling pathway. The top 10 hub genes were FN1, COL1A2, SPARC, COL3A1, CTGF, LUM, TIMP1, THBS2, COL5A2, and TGFB1.ConclusionsIn summary, key candidate genes and pathways were identified by using integrated bioinformatics analysis, which may provide insights into the underlying mechanisms and offer potential target genes for the treatment of IDD.
| S-EPMC7465721 | biostudies-literature
Project description: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.
| S-EPMC7875098 | biostudies-literature
Project description:BackgroundLumbar disc degeneration (LDD) is an important pathological basis for the development of degenerative diseases of the lumbar spine. Most clinical patients have low back pain as their main symptom. The deterioration of the biomechanical environment is an important cause of LDD. Although there is a large amount of basic research on LDD, there are fewer reports that correlate biomechanical mechanisms with basic research. Our research aims to identify 304 key genes involved in LDD due to biomechanical deterioration, using a bioinformatics approach. We focus on SMAD3, CAV1, SMAD7, TGFB1 as hub genes, and screen for 30 potential target drugs, offering novel insights into LDD pathology and treatment options.MethodsThe Gene Cards, GenCLip3, OMIM and Drugbank databases were explored to obtain genes associated with biomechanics and LDD, followed by making veen plots to obtain both co-expressed genes. GO enrichment analysis and KEGG pathway analysis of the co-expressed genes were obtained using the DAVID online platform and visualised via a free online website. Protein interaction networks (PPI) were obtained through the STRING platform and visualised through Cytoscape 3.9.0. These genes were predicted for downstream interaction networks using the STITCH platform. Then, the GSE56081 dataset was used to validate the key genes. RT-PCR was used to detect mRNA expression of core genes in the degenerated nucleus pulposus (NP) samples and western bolt was used for protein expression. Lastly, the obtained hub genes were searched in the drug database (DGIdb) to find relevant drug candidates.ResultsFrom the perspective of biomechanics-induced LDD, we obtained a total of 304 genes, the GO functional enrichment and KEGG pathway enrichment analysis showed that the functions of these genes are mostly related to inflammation and apoptosis. The PPI network was constructed and four Hub genes were obtained through the plug-in of Cytoscape software, namely SMAD3, CAV1, SMAD7 and TGFB1. The analysis of key genes revealed that biomechanical involvement in LDD may be related to the TGF-β signaling pathway. Validation of the GSE56081 dataset revealed that SMAD3 and TGFB1 were highly expressed in degenerating NP samples. RT-PCR results showed that the mRNA expression of SMAD3 and TGFB1 was significantly increased in the severe degeneration group; Western blot results also showed that the protein expression of TGFB1 and P-SMAD3 was significantly increased. In addition, we identified 30 potential drugs.ConclusionThis study presented a new approach to investigate the correlation between biomechanical mechanisms and LDD. The deterioration of the biomechanical environment may cause LDD through the TGF-β signaling pathway. TGFB1 and SMAD3 are important core targets. The important genes, pathways and drugs obtained in this study provided a new basis and direction for the study, diagnosis and treatment of LDD.
| S-EPMC10920361 | biostudies-literature
Project description:BackgroundInflammation and immune factors are the core of intervertebral disc degeneration (IDD), but the immune environment and epigenetic regulation process of IDD remain unclear. This study aims to identify immune-related diagnostic candidate genes for IDD, and search for potential pathogenesis and therapeutic targets for IDD.MethodsGene expression datasets were obtained from the Gene Expression Omnibus (GEO). Differential expression immune genes (Imm-DEGs) were identified through weighted gene correlation network analysis (WGCNA) and linear models for microarray data analysis (Limma). LASSO algorithm was used to identify feature genes related to IDD, which were compared with core node genes in PPI network to obtain hub genes. Based on the coefficients of hub genes, a risk model was constructed, and the diagnostic value of hub genes was further evaluated through receiver operating characteristic (ROC) analysis. Xcell, an immunocyte analysis tool, was used to estimate the infiltration of immune cells. Finally, nucleus pulposus cells were co-cultured with macrophages to create an M1 macrophage immune inflammatory environment, and the changes of hub genes were verified.ResultsCombined with the results of WGCNA and Limma gene differential analysis, a total of 30 Imm-DEGs were identified. Imm-DEGs enriched in multiple pathways related to immunity and inflammation. LASSO algorithm identified 10 feature genes from Imm-DEGs that significantly affected IDD, and after comparison with core node genes in the PPI network of Imm-DEGs, 6 hub genes (NR1H3, SORT1, PTGDS, AGT, IRF1, TGFB2) were determined. Results of ROC curves and external dataset validation showed that the risk model constructed with the 6 hub genes had high diagnostic value for IDD. Immunocyte infiltration analysis showed the presence of various dysregulated immune cells in the degenerative nucleus pulposus tissue. In vitro experimental results showed that the gene expression of NR1H3, SORT1, PTGDS, IRF1, and TGFB2 in nucleus pulposus cells in the immune inflammatory environment was up-regulated, but the change of AGT was not significant.ConclusionsThe hub genes NR1H3, SORT1, PTGDS, IRF1, and TGFB2 can be used as immunorelated biomarkers for IDD, and may be potential targets for immune regulation therapy for IDD.
| S-EPMC11315086 | biostudies-literature
Project description:The exact mechanisms associated with secondary brain damage following traumatic brain injury (TBI) remain unclear; therefore, identifying the critical molecular mechanisms involved in TBI is essential. The mRNA expression microarray GSE2871 was downloaded from the Gene Expression Omnibus (GEO) repository. GSE2871 comprises a total of 31 cerebral cortex samples, including two post-TBI time points. The microarray features eight control and seven TBI samples, from 4 hours post-TBI, and eight control and eight TBI samples from 24 hours post-TBI. In this bioinformatics-based study, 109 and 66 differentially expressed genes (DEGs) were identified in a Sprague-Dawley (SD) rat TBI model, 4 and 24 hours post-TBI, respectively. Functional enrichment analysis showed that the identified DEGs were significantly enriched in several terms, such as positive regulation of nuclear factor-κB transcription factor activity, mitogen-activated protein kinase signaling pathway, negative regulation of apoptotic process, and tumor necrosis factor signaling pathway. Moreover, the hub genes with high connectivity degrees were primarily related to inflammatory mediators. To validate the top five hub genes, a rat model of TBI was established using the weight-drop method, and real-time quantitative polymerase chain reaction analysis of the cerebral cortex was performed. The results showed that compared with control rats, Tnf-α, c-Myc, Spp1, Cxcl10, Ptprc, Egf, Mmp9, and Lcn2 were upregulated, and Fn1 was downregulated in TBI rats. Among these hub genes, Fn1, c-Myc, and Ptprc may represent novel biomarkers or therapeutic targets for TBI. These identified pathways and key genes may provide insights into the molecular mechanisms of TBI and provide potential treatment targets for patients with TBI. This study was approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Nanchang University, China (approval No. 003) in January 2016.
| S-EPMC7749465 | biostudies-literature
Project description:Intervertebral disc degeneration (IVDD) has been considered a major cause of low back pain. Therefore, further molecular subtypes of IVDD and identification of potential critical genes are urgently needed. First, consensus clustering was used to classify patients with IVDD into two subtypes and key module genes for subtyping were identified using weighted gene co-expression network analysis (WGCNA). Then, key module genes for the disease were identified by WGCNA. Subsequently, SVM and GLM were used to identify hub genes. Based on the above genes, a nomogram was constructed to predict the subtypes of IVDD. Finally, we find that ROM1 is lowered in IVDD and is linked to various cancer prognoses. The present work offers innovative diagnostic and therapeutic biomarkers for molecular subtypes of IVDD.
| S-EPMC11006460 | biostudies-literature
Project description:Although the pathology of sciatica has been studied extensively, the transcriptional changes in the peripheral blood caused by sciatica have not been characterized. An Agilent SurePrint G3 human gene expression microarray 8 ╳ 60 K was used to analyse gene expression in whole blood from patients with sciatica compared with healthy volunteers.
2021-01-22 | GSE150408 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-05 | GSE230809 | GEO
Project description:Background and objectiveIntervertebral disc degeneration (IDD) is a complex multifactorial and irreversible pathological process. In IDD, multiple competing endogenous RNAs (ceRNA, including mRNA, lncRNA, and pseudogenes) can compete to bind with miRNAs. However, the potential metabolic signatures in nucleus pulposus (NP) cells remain poorly understood. This study investigated key metabolic genes and the ceRNA regulatory mechanisms in the pathogenesis of IDD based on microarray datasets.MethodsWe retrieved and downloaded four independent IDD microarray datasets from the Gene Expression Omnibus. Combining the predicted interactions from online databases (miRcode, miRDB, miRTarBase, and TargetScan), differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were identified. A ceRNA network was constructed and annotated using GO and KEGG pathway enrichment analyses. Moreover, we searched the online metabolic gene set and used support vector machine (SVM) to find the critical metabolic DEmRNA(s) and other DERNAs. Differential gene expression was validated with a merged dataset.ResultsA total of 45 DEmRNAs, 36 DElncRNAs, and only one DEmiRNA (miR-338-3p) were identified in the IDD microarray datasets. GO and KEGG pathway enrichment analyses revealed that the DEmRNAs were predominantly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, apoptosis, and cellular response to oxidative stress. Based on SVM screening, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK/FBPase) 2 is the critical metabolic gene with lower expression in IDD, and AC063977.6 is the key lncRNA with lower expression in IDD. The ceRNA hypothesis suggests that AC063977.6, miR-338-3p (high expression), and PFKFB2 are dysregulated as an axis in IDD.ConclusionsThe results suggest that lncRNA AC063977.6 correlate with PFKFB2, the vital metabolic signature gene, via targeting miR-338-3p during IDD pathogenesis. The current study may shed light on unraveling the pathogenesis of IDD.
| S-EPMC7937257 | biostudies-literature
Project description:Intervertebral disc degeneration
| PRJNA962588 | ENA