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Updated: May 20, 2025

A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
Published on: February 14, 2021
The Significance of MAPK Signaling Pathway in the Diagnosis and Subtype Classification of Intervertebral Disc
Yong Liu1, Xueyan Chen2, Jingwen Chen1
1Department of Orthopedics, The Affiliated Hospital of Traditional Chinese Medicine Southwest Medical University Luzhou China.
Background:
Intervertebral disc degeneration (IDD) is a human aging disease related mainly to inflammation, cellular senescence, RNA/DNA methylation, and ECM. The mitogen-activated protein kinase (MAPK) signaling pathway is engaged in multiple biological functions by phosphorylating specific serine and threonine residues on target proteins through phosphorylation cascade effects, but the role and specific mechanisms of the MAPK signaling pathway in IDD are still unclear.
Methods:
We identified 20 MAPK-related differential genes by differential analysis of the GSE124272 and GSE150408 datasets from the GEO database. To explore the biological functions of these differential genes in humans, we performed GO and KEGG analyses. Additionally, we applied PPI networks, LASSO analysis, the RF algorithm, and the SVM-RFE algorithm to identify core MAPK-related genes. Finally, we conducted further validation using clinical samples.
Results:
We ultimately identified and validated four pivotal MAPK-related genes, namely, KRAS, JUN, RAP1B, and TNF, using clinical samples, and constructed the ROC curves to evaluate the predictive accuracy of the hub genes. A nomogram model was subsequently developed based on these four hub MAPK genes to predict the prevalence of IDD. Based on these four hub genes, we classified IDD patients into two MAP clusters by applying the consensus clustering method and identified 1916 DEGs by analyzing the differences between the two clusters. Further analysis using the same approach allowed us to identify two gene clusters based on these DEGs. We used a PCA algorithm to determine the MAPK score for each sample and discovered that MAPK cluster A and gene cluster A had higher scores, suggesting greater sensitivity to MAPK signaling pathway-associated agents in the subtype. We displayed the differing expression levels of four hub MAPK-related genes across the two clusters and their relationship with immune cell infiltration to highlight the distinctions between clusters A and B.
Conclusion:
In summary, four hub MAPK signaling pathway-related genes, KRAS, JUN, RAP1B, and TNF, could be applied to the diagnosis and subtype classification of IDD and benefit the prevention and treatment of IDD.
Insights
Four key genes (KRAS, JUN, RAP1B, TNF) in the MAPK signaling pathway were identified as crucial for intervertebral disc degeneration (IDD). These genes aid in diagnosing IDD and classifying patient subtypes for targeted treatment.
Area of Science:
- Biomedical Science
- Molecular Biology
- Genetics
Background:
- Intervertebral disc degeneration (IDD) is a common aging disease linked to inflammation, cellular senescence, and epigenetic modifications.
- The precise role of the mitogen-activated protein kinase (MAPK) signaling pathway in IDD pathogenesis remains largely undefined.
Purpose of the Study:
- To identify and validate key MAPK signaling pathway-related genes involved in intervertebral disc degeneration (IDD).
- To explore the diagnostic and prognostic potential of these genes in IDD.
- To classify IDD subtypes based on MAPK pathway gene expression.
Main Methods:
- Differential gene expression analysis of public datasets (GSE124272, GSE150408).
- Gene Ontology (GO) and KEGG pathway analyses.
- Network analysis (PPI), LASSO, Random Forest (RF), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms.
- Clinical sample validation, ROC curve analysis, nomogram construction, and consensus clustering.
Main Results:
- Four pivotal MAPK-related genes (KRAS, JUN, RAP1B, TNF) were identified and validated in clinical samples.
- A nomogram model was developed for predicting IDD prevalence based on these four genes.
- IDD patients were classified into two clusters (MAPK cluster A and B) based on these genes, revealing distinct molecular and immune infiltration profiles.
Conclusions:
- The identified hub genes KRAS, JUN, RAP1B, and TNF are potential diagnostic and prognostic biomarkers for IDD.
- These genes facilitate IDD subtype classification, paving the way for personalized prevention and treatment strategies.
- Understanding the MAPK pathway's role offers new therapeutic targets for mitigating IDD progression.
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