Identification of Immune-Related Hub Genes in Parkinson's Disease

Background: Parkinson's disease (PD) is a common, age-related, and progressive neurodegenerative disease. Growing evidence indicates that immune dysfunction plays an essential role in the pathogenic process of PD. The objective of this study was to explore potential immune-related hub genes and immune infiltration patterns of PD.Method: The microarray expression data of human postmortem substantia nigra samples were downloaded from GSE7621, GSE20141, and GSE49036. Key module genes were screened via weighted gene coexpression network analysis, and immune-related genes were intersected to obtain immune-key genes. Functional enrichment analysis was performed on immune-key genes of PD. In addition to, immune infiltration analysis was applied by a single-sample gene set enrichment analysis algorithm to detect differential immune cell types in the substantia nigra between PD samples and control samples. Least absolute shrinkage and selection operator analysis was performed to further identify immune-related hub genes for PD. Receiver operating characteristic curve analysis of the immune-related hub genes was used to differentiate PD patients from healthy controls. Correlations between immune-related hub genes and differential immune cell types were assessed.Result: Our findings identified four hub genes (SLC18A2, L1CAM, S100A12, and CXCR4) and seven immune cell types (neutrophils, T follicular helper cells, myeloid-derived suppressor cells, type 1 helper cells, immature B cells, immature dendritic cells, and CD56 bright natural killer cells). The area under the curve (AUC) value of the four-gene-combined model was 0.92. The AUC values of each immune-related hub gene (SLC18A2, L1CAM, S100A12, and CXCR4) were 0.81, 0.78, 0.78, and 0.76, respectively.Conclusion: In conclusion, SLC18A2, L1CAM, S100A12, and CXCR4 were identified as being associated with the pathogenesis of PD and should be further researched.

Automated summary

This study identified four hub genes (SLC18A2, L1CAM, S100A12, and CXCR4) and seven immune cell types (neutrophils, T follicular helper cells, myeloid-derived suppressor cells, type 1 helper cells, immature B cells, immature dendritic cells, and CD56 bright natural killer cells) associated with the pathogenesis of PD. The combined model of the four genes showed a high accuracy in differentiating PD patients from healthy controls.