Identification of immunological characteristics and cuproptosis-related molecular clusters in Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by progressive articular damage, functional loss, and comorbidities. The relationship between cuproptosis, a form of programmed cell death, and RA remains unknown. Therefore, this study aimed to explore cuproptosis-related molecular clusters in RA. Gene expression profiles of GSE93272 were downloaded from the Gene Expression Omnibus to identify the expression profiles of cuproptosis regulators and the immune infiltration characteristics of RA. The molecular clusters of cuproptosis-related genes and the related immune cell infiltration were explored. Cluster-specific differentially expressed genes were identified using the weighted gene co-expression network analysis. Further, an external dataset (GSE15573) was used, and an enzyme-linked immunosorbent assay was performed to validate the predictive efficiency. Thirteen cuproptosis-related genes and activated immune responses were identified between patients with RA and controls. Immune infiltration revealed significant immunological heterogeneity in the two cuproptosis-related molecular clusters in RA. Functional enrichment indicated that Cluster1 and Cluster2 were predominantly enriched in the toll-like receptor signalling pathway and regulation of autophagy, respectively. Further, the performance of FAM96A and CGRRF1 genes in the external validation dataset was observed to be relatively satisfactory (area under the receiver operating characteristic curve = 0.687 and 0.674, respectively). Based on our serum samples, FAM96A and CGRRF1 both exhibited higher expression levels in patients with RA (p = 0.001; p = 0.000). Our study systematically illustrated the involvement of cuproptosis in the progression of RA, and explored the pathogenic mechanisms and novel therapeutic strategies for RA, targeting FAM96A and CGRRF1.