Integrative bioinformatics analysis of shared genetic signatures and biological mechanisms of obesity and lumbar disc herniation

AN Jianpeng; WANG Fei; WANG Yarong; MENG Zhaoning; LIU Hongbo; MU Naiqi; DONG Zunan; FENG Wei

doi:10.3969/j.issn.2097-1753.2024.02.011

Abstract：Objective To analyze the shared gene signatures and biological mechanisms of obesity and lumbar disc herniation using bioinformatics methods in order to provide new targets for related treatments.Methods The dataset of obesity and lumbar disc herniation was downloaded from the Gene Expression Omnibus(GEO)database while the differentially co-expressed genes of obesity and lumbar disc herniation were obtained by analysis.These genes were analyzed via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then,a protein-protein interaction(PPI)network was constructed using the search tool for recurring instances of neighboring genes(STRING)database and the hub genes in the network were detected and intersected with the ferroptosis gene set.Differences in immune cell infiltration between the obese and normal control and between lumbar disc herniation and normal control were identified using single-sample gene get enrichment analysis(ssGSEA).Micro ribonucleic acids(miRNAs)associated with obesity and lumbar disc herniation and their corresponding target genes were obtained via the human microRNA disease database(HMDD)and StarBase databases.Finally,the miRNAs-mRNAs regulatory network associated with these two diseases was constructed by using the intersection of previously obtained target genes and shared genes.Results A total of 250 differentially co-expressed genes were screened in GSE15653 and GSE124272.Functional enrichment analysis indicated that signal transduction,responses to endoplasmic reticulum stress,exosomes,cytoplasm,proteins,and protein kinase binding might be associated with obesity and lumbar disc herniation.KEGG enrichment analysis indicated that tumor necrosis factor(TNF)signaling pathway and phosphatidyl-inositol 3-kinase/serine-threonine kinase(PI3K-Akt)signaling pathway were possibly involved in the mechanism of obesity-induced lumbar disc herniation.The construction of the PPI network indicated that the mechanism between obesity and lumbar disc herniation might be closely related to such target genes as JUN,HIF1A,ALDH18A1,MCM6,DLGAP5,BARD1 and WRN.Conclusion The shared key genes and pathways between obesity and lumbar disc herniation are identified,which can shed light on the common pathogenesis and potential therapeutic targets of obesity and lumbar disc herniation.