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.

JOR Spine
|March 26, 2025
PubMed
Abstract

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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