Bioinformatics analysis of cuproptosis key gene dihydrolipoyl dehydrogenase in spinal cord injury
Objective Bioinformatics was used to analyze the differential expression of dihydroli-poamide dehydrogenase(DLD),a key gene for cuproptosis,in patients with spinal cord injury,and to ex-plore its relationship with the immune microenvironment and related signaling pathways.Methods The high throughput gene expression omnibus(GEO)was used to obtain the relevant data set of spinal cord in-jury patients.R language was used to analyze the expression difference of key genes of copper death be-tween the control group and the spinal cord injury group in this dataset.According to the American Spinal Injury Association(ASIA),the spinal cord injury group was divided into mild spinal cord injury group and severe spinal cord injury group.R-language was used to analyze the difference in DLD expression between the control group and patients with different spinal cord injury classification.Immunocell infiltration analy-sis was used to investigate the correlation between DLD and different types of immunoinfiltrating cells in pa-tients with spinal cord injury.The genes associated with DLD were screened using STRING database,and gene set enrichment analysis(GSEA)was performed.Independent-sample t-test was used to compare measurement data between groups.Results The expressions of DLD and MTF1 in spinal cord injury group(1.51±0.12,1.83±0.14)were significantly higher than those in control group(1.24±0.11,1.47±0.13,t=8.58,P<0.05,t=9.12,P<0.05).The expressions of LIPT1,LIAS,GLS and FDX1 in the spinal cord injury group(0.97±0.09,0.17±0.02,0.81±0.08,0.69±0.06)were significantly lower than those in the control group(1.21±0.10,0.30±0.03,1.02±0.07,0.94±0.07,t=7.67,P<0.05,t=14.72,P<0.05,t=7.88,P<0.05,t=11.21,P<0.05).The expression level of DLD in mild spinal cord injury group(1.44±0.12)was significantly higher than that in control group(1.24±0.11,t=6.83,P<0.05).The expression level of DLD in the severe spinal cord injury group(1.62±0.14)was significantly higher than that in the mild spinal cord injury group(1.44±0.12,t=6.35,P<0.05).Correlation analysis showed that DLD was positively correlated with M2 macrophage(R=0.36,P=7.5e-03),and negatively correlated with CD8+T cells and naive CD4+T cell were negatively correla-ted(R=-0.42,P<0.05 R=-0.40,P<0.05).The STRING analysis shows that,the 10 key interac-ting genes of DLD are DLAT,PDHB,PDHA1,PDHX,BCKDHA,BCKDHB,DLST,DBT,OGDH and AMT.The results of GO and KEGG analysis showed that DLD plays an important role mainly through tri-carboxylic acid cycle,pyruvate metabolism,acetyl-CoA synthesis and metabolism,branched-chain amino acid degradation,and histone succinylation.Conclusion DLD is highly expressed in patients with spinal cord injury,and is closely related to the severity of spinal cord injury and immune microenvironment.In-depth exploration of the functional proteins and signaling pathways related to DLD is of great significance for the study of the pathological mechanism and clinical treatment of spinal cord injury.