Identification and validation of key genes related to arginine methylation modification in sepsis using transcriptome combined with Mendelian randomization analysis

Background: Patients with sepsis often exhibit a decrease in lymphatic numbers, which can be facilitated by protein arginine methyltransferase (PRMT). However, it is unclear how PRMT contributes to lymphopenia in sepsis. Methods: This study employed the sepsis-related datasets (GSE65682 and GSE134347) and 9 PRMT genes. Firstly, we intersected the differentially expressed genes (DEGs) with weighted gene co-expression network analysis (WGCNA) module genes to identify DE-PRMT-related genes (DE-PRMT-RGs). Thereafter, candidate key genes were obtained after Mendelian randomization (MR) analysis and machine learning screening. Eventually, we subjected key genes identified by expression analysis and receiver operating characteristic (ROC) curves to gene set enrichment analysis (GSEA), immune infiltration analysis, immune checkpoint analysis, molecular docking, regulatory networks construction, and nomogram development. Results: We firstly intersected 4,246 DEGs with 1,884 PRMT scoring module genes to obtain 969 DE-PRMT-RGs. Further MR analysis and machine learning jointly identified 5 candidate genes ( CRLF3 , ELAC2 , PBX2 , MCTP2 , and EMB ). Among these, ELAC2 , PBX2 , MCTP2 , and EMB demonstrated consistent expression trends, with the area under the curve (AUC) values of the ROC curve exceeding 0.7 in GSE65682 and GSE134347. Therefore, they were defined as key PRMT-related genes. The GSEA analysis showed enrichment in cytoplasmic translation ( ELAC2 , MCTP2 ), non-coding RNA metabolism ( EMB ), and metabolic processes ( PBX2 ). The immune infiltration analysis revealed a significant correlation between PBX2 and neutrophils, as well as between ELAC2 / MCTP2 / EMB with activated NK cells, CD8+ T cells. Conclusion: In this study, ELAC2 , PBX2 , MCTP2 and EMB were identified as key genes related to PRMT for sepsis, which provided a theoretical basis for the study of sepsis.