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The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Predicted Immune-Related Genes and Subtypes in Systemic Lupus Erythematosus Based on Immune Infiltration Analysis
Lin Xu1, Xiaoyan Su2, Zhongcheng Liu3
1Department of Nephrology, The Affiliated Taian City Centeral Hospital of Qingdao University, Tai'an 271000, Shandong Province, China.
Objective:
The present investigation is aimed at identifying key immune-related genes linked with SLE and their roles using integrative analysis of publically available gene expression datasets.
Methods:
Four gene expression datasets pertaining to SLE, 2 from whole blood and 2 experimental PMBC, were sourced from GEO. Shared differentially expressed genes (DEG) were determined as SLE-related genes. Immune cell infiltration analysis was performed using CIBERSORT, and case samples were subjected to k-means cluster analysis using high-abundance immune cells. Key immune-related SLE genes were identified using correlation analysis with high-abundance immune cells and subjected to functional enrichment analysis for enriched Gene Ontology Biological Processes and KEGG pathways. A PPI network of genes interacting with the key immune-related SLE genes was constructed. LASSO regression analysis was performed to identify the most significant key immune-related SLE genes, and correlation with clinicopathological features was examined.
Results:
309 SLE-related genes were identified and found functionally enriched in several pathways related to regulation of viral defenses and T cell functions. k-means cluster analysis identified 2 sample clusters which significantly differed in monocytes, dendritic cell resting, and neutrophil abundance. 65 immune-related SLE genes were identified, functionally enriched in immune response-related signaling, antigen receptor-mediated signaling, and T cell receptor signaling, along with Th17, Th1, and Th2 cell differentiation, IL-17, NF-kappa B, and VEGF signaling pathways. LASSO regression identified 9 key immune-related genes: DUSP7, DYSF, KCNA3, P2RY10, S100A12, SLC38A1, TLR2, TSR2, and TXN. Imputed neutrophil percentage was consistent with their expression pattern, whereas anti-Ro showed the inverse pattern as gene expression.
Conclusions:
Comprehensive bioinformatics analyses revealed 9 key immune-related genes and their associated functions highly pertinent to SLE pathogenesis, subtypes, and identified valuable candidates for experimental research.
