Emerging evidence shows that carotid atherosclerosis is related to the activation of immune-related pathways and inflammatory cell infiltration. However, the immune-linked pathways that helped in the advancement of the carotid atherosclerotic plaque and the association of such plaques with the infiltration status of the body’s immune cells still unclear. Here, the expression profiles of the genes expressed during the progression of the carotid atherosclerotic plaques were retrieved from the Gene Expression Omnibus database and 178 differentially expressed genes were examined. The Weighted Gene Coexpression Network Analysis technique identified one of the brown modules showed the greatest correlation with carotid atherosclerotic plaques. In total, 66 intersecting genes could be detected after combining the DEGs. LASSO regression analysis was subsequently performed to obtain five hub genes as potential biomarkers for carotid atherosclerotic plaques. The functional analysis emphasized the vital roles played by the inflammation- and immune system-related pathways in this disease. The immune cell infiltration results highlighted the significant correlation among the CD4+ T cells, B cells, macrophages, and CD8+ T cells. Thereafter, the gene expression levels and the diagnostic values related to every hub gene were further validated. The above results indicated that macrophages, B cells, CD4+ T cells, and CD8 + T cells were closely related to the formation of the advanced-stage carotid atherosclerotic plaques. Based on the results, it could be hypothesized that the expression of hub genes (C3AR1, SLAMF8, TMEM176A, FERMT3, and GIMAP4) assisted in the advancement of the early-stage to advanced-stage carotid atherosclerotic plaque through immune-related signaling pathways. This may help to provide novel strategies for the treatment of carotid plaque in the context of predictive, preventive, and personalized medicine.

Background: Interleukin-1 receptor antagonist (IL1RN) has been reported as a biomarker of many cancers. However, the biological function of IL1RN in papillary thyroid carcinoma (PTC) remains undetermined.Methods: We obtained IL1RN expression data from The Cancer Genome Atlas (TCGA) database. Enrichment analysis of coexpressed genes and IL1RN methylation analysis were performed via LinkedOmics. The correlations between IL1RN and immune infiltrates were investigated via ESTIMATE, TIMER and TISIDB. We analyzed the association of IL1RN expression with pancancer overall survival (OS) via Gene Expression Profiling Interactive Analysis (GEPIA).Results: IL1RN showed higher expression levels and lower methylation levels in PTC tissues than in normal tissues. Higher IL1RN expression was significantly associated with shorter progression-free survival (PFS), advanced tumor stage, tumor metastasis, increased incidence of BRAF mutations, and decreased incidence of N-RAS and H-RAS mutations. Genes coexpressed with IL1RN participate primarily in immune-related pathways. IL1RN expression was positively correlated with immune infiltration, tumor progression and poor overall survival for all cancers.Conclusions: IL1RN is a good prognostic and diagnostic biomarker for PTC. IL1RN may promote thyroid cancer progression through immune-related pathways. Methylation may act as an upstream regulator of IL1RN expression and biological function. Additionally, IL1RN was shown to have broad prognostic value in a pancancer cohort.