Oxidative stress-related genes and molecular mechanisms after spinal cord injury:data analysis and verification based on GEO database
- VernacularTitle:脊髓损伤后氧化应激相关基因及分子机制:基于GEO数据库的数据分析及验证
- Author:
Ziheng WANG
1
;
Shuang WU
1
Author Information
- Publication Type:Journal Article
- Keywords: spinal cord injury; oxidative stress; differentially expressed gene; bioinformatics; biomarker; engineered tissue construction
- From: Chinese Journal of Tissue Engineering Research 2025;29(32):6893-6904
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:The biological significance of oxidative stress in spinal cord injury has not been systematically investigated.OBJECTIVE:To investigate the role of oxidative stress-related genes in the development of spinal cord injury and to elucidate the related molecular mechanisms.METHODS:The GSE151371 dataset was obtained from the Gene Expression Omnibus(GEO)database and selected a gene set highly relevant to oxidative stress from the GeneCards database(including 899 genes with relevance scores of no less than 7).Firstly,we performed differential expression gene analysis on samples from spinal cord injury patients and healthy controls.Subsequently,we cross-referenced these 899 oxidative stress genes with the differential expression genes to identify oxidative stress-related genes closely associated with spinal cord injury(spinal cord injury-reactive oxygen species-related genes).Then,the Least Absolute Shrinkage and Selection Operator and Support Vector Machine-Recursive Feature Elimination algorithms were used to derive potential biomarkers based on the spinal cord injury-reactive oxygen species-related genes.Following this,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses on these biomarkers were conducted to explore their roles in biological processes and the signaling pathways they participate in.Additionally,we constructed a competing endogenous RNA network and performed an in-depth analysis of the immune microenvironment.We predicted transcription factors related to these biomarkers and explored potential therapeutic drugs.Finally,fifteen blood samples from eight patients with acute spinal cord injury and seven controls were collected from Affiliated Hospital of Guizhou Medical University for reverse transcription quantitative polymerase chain reaction analysis to evaluate the expression of biomarkers between spinal cord injury and control samples.RESULTS AND CONCLUSION:(1)There were 2 511 differential expression genes between spinal cord injury and control samples.Cross-analysis of oxidative stress genes and differential expression gene resulted in 151 spinal cord injury-reactive oxygen species-related genes.Least Absolute Shrinkage and Selection Operator and Support Vector Machine-Recursive Feature Elimination identified six biomarkers-S100A9,PLAU,CASP4,GAPDH,CYP1B1,and HSPA1B-involved in activities such as nicotinamide adenine dinucleotide phosphate oxidoreductase activity and oxidative phosphorylation.(2)Six messenger RNAs(mRNAs),eight microRNAs(miRNAs),and 50 long noncoding RNAs(lncRNAs)formed the mRNA-miRNA-lncRNA network,including relationships such as S100A9-hsa-mir-16-5p-HCG18 and CYP1B1-hsa-mir-429-KCNQ1OT1.(3)Infiltration levels of nine immune cells,including plasma cells,resting natural killer cells,and M0 macrophages,showed significant differences between spinal cord injury and control samples.(4)The top five predicted transcription factors were FOSB,ZNF581,SP110,NFIL3,and BATF2,with ZNF581 and NFIL3 showing significant expression differences between spinal cord injury and control samples.(5)The study predicted a variety of drugs based on the six biomarkers,and the molecular docking results showed that β-naphthoflavone had good binding activity to the target protein of CYP1B1.The interaction pairs they formed included DB01373-S100A9 and DB01065-CYP1B1.(6)In reverse transcription quantitative polymerase chain reaction verification,S100A9,GAPDH,CYP1B1,and HSPA1B showed significant differences between spinal cord injury and control groups,while PLAU and CASP4 showed an increasing trend in spinal cord injury group.(7)This study identified six key biomarkers,including S100A9,PLAU,CASP4,GAPDH,CYP1B1,and HSPA1B,and subsequently predicted 100 small-molecule drugs based on these biomarkers.These findings provide valuable insights for health management and disease prevention among the Chinese population,offering new perspectives for spinal cord injury treatment options.
