Comprehensive landscape of immune-based classifier related to early diagnosis and macrophage M1 in spinal cord injury

Numerous studies have documented that immune responses are crucial in the pathophysiology of spinal cord injury (SCI). Our study aimed to uncover the function of immune-related genes (IRGs) in SCI. Here, we comprehensively evaluated the transcriptome data of SCI and healthy controls (HC) obtained from the GEO Database integrating bioinformatics and experiments. First, a total of 2067 DEGs were identified between the SCI and HC groups. Functional enrichment analysis revealed substantial immune-related pathways and functions that were abnormally activated in the SCI group. Immune analysis revealed that myeloid immune cells were predominantly upregulated in SCI patients, while a large number of lymphoid immune cells were dramatically downregulated. Subsequently, 51 major IRGs were screened as key genes involved in SCI based on the intersection of the results of WGCNA analysis, DEGs, and IRGs. Based on the expression profiles of these genes, two distinct immune modulation patterns were recognized exhibiting opposite immune characteristics. Moreover, 2 core IRGs (FCER1G and NFATC2) were determined to accurately predict the occurrence of SCI via machine learning. qPCR analysis was used to validate the expression of core IRGs in an external independent cohort. Finally, the expression of these core IRGs was validated by sequencing, WB, and IF analysis in vivo. We found that these two core IRGs were closely associated with immune cells and verified the co-localization of FCER1G with macrophage M1 via IF analysis. Our study revealed the key role of immune-related genes in SCI and contributed to a fresh perspective for early diagnosis and treatment of SCI.