Moreover, the functional enrichment and annotation demonstrated that the first module was significantly associated with PI3K-Akt signaling pathway (P = 0.02) and GTPase mediated signal transduction (P = 0.003), and the second one was involved in Insulin-like growth factor receptor signaling pathway (P = 0.02), which can potentially regulate the major pathological changes during RA progression and have also been indicated as therapeutic targets of this disease (Malemud, 2015; Alunno et al., 2017; Cheung and McInnes, 2017; Figure 3A). This evidence concerns the gene AKT1 and rheumatoid arthritis.