The significance of MAPK signaling pathway in the diagnosis and subtype classification of intervertebral disc degeneration

Abstract

Abstract 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. We obtained 20 MAPK-related differential genes by differential analysis of GSE124272 and GSE150408 derived from the GEO database. To investigate the biological function of this differential gene in humans, we also performed GO and KEGG analyses. We applied PPI networks, LASSO analysis, the RF algorithm, and the SVM-RFE algorithm to identify core MAPK-related genes. We eventually obtained four hub MAPK-related genes, namely KRAS, JUN, and RAP1B, and constructed the ROC curves separately to evaluate the precision of the hub genes. To forecast the prevalence of IDD, a nomogram model was created on our four hub MAPK genes of choice. Based on these 4 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. Then, using the same method, we identified two gene clusters based on these DEGs. We used a PCA algorithm to determine the MAPK score for each sample, and in the end, we discovered that MAPK cluster A and gene cluster A had higher scores. 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. 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.