Identification of Hub Genes and Pathways Associated with Oxidative Stress and Cell Senescence of intervertebral disc between Disc Herniation and Degenerative Spondylolisthesis Using Bioinformatics Analysis

Abstract

AbstractBackground This study aimed to identify the hub genes and pathways of genes related to oxidative stress (OS) and cell senescence (CS) of intervertebral disc between disc herniation (DH) and degenerative spondylolisthesis (DS), and to predict the transcription factors of the hub genes. Methods The GSE146904 dataset was obtained from the Gene Expression Omnibus (GEO) database, including 5 disc herniation samples and 5 degenerative spondylolisthesis samples, and the differentially expressed genes (DEGs) were recognized by TBtools. Genes related to oxidative stress in the Gene Ontology (GO) database and genes related to cell senescence in the CellAge database were obtained. By using DAVID, Metascape, and GSEA, GO and signaling pathways analysis were performed. Protein-protein interaction (PPI) network was constructed using the STRING database, and the degree algorithm of Cytoscape software was used to screen for the hub genes. The NetworkAnalyst web tool was used to find the hub genes’ transcriptional factors (TFs). Results 428 oxidative stress–related genes were obtained in GSE146904 and GO database, among which 33 genes were significantly differentially expressed. 267 cell senescence–related genes were obtained in GSE146904 and CellAge database, among which 18 genes were significantly differentially expressed. OS-related genes were primarily involved in several signaling pathways, such as Calcium signaling pathway and GnRH signaling pathway. The top 10 hub genes were JUN, FOXO3, CASP3, JAK2, RELA, EZH2, ABL1, PTGS2, FBXW7, MCL1. Besides, TFAP2A, GATA2 and SP1. Besides, NFIC and FOXC1 might be the key regulatory factors of hub genes. Meanwhile, CS-related genes were primarily involved in MAPK signaling pathways. The top 10 hub genes were MAPK12, BLK, CAV1, CDK18, PIM1, CXCL1, NOTCH3, NUAK1, MAP3K6 and MAP4K1. Besides, GATA2, FOXC1 and SREBF1 might be the key regulatory factors of hub genes. Conclusions Some hub genes and signaling pathways associated with oxidative stress and cell senescence between DS and DH were identified through a series of bioinformatics analyses. This may play a potential role in explaining disease progression and treatment.