Identification of potential hub genes and biological mechanism in rheumatoid arthritis and non-small cell lung cancer via integrated bioinformatics analysis

Although there is evidence of the association between RA and NSCLC, little is known about their interaction mechanisms. The aim of this study is to identify potential hub genes and biological mechanism in RA and NSCLC via integrated bioinformatics analysis. The gene expression datasets of RA and NSCLC were downloaded to discover and validate hub genes. After identifying DEGs, we performed enrichment analysis, PPI network construction and module analysis, selection and validation of hub genes. Moreover, we selected the hub gene PTPRC for expression and prognosis analysis, immune analysis, mutation and methylation analysis in NSCLC. Finally, we performed real-time PCR, colony formation assay, wound healing assay, transwell invasion assay, sphere formation assay and western blotting to validate the role of PTPRC in A549 cells. We obtained 320 DEGs for subsequent analysis. Enrichment results showed that the DEGs were mainly involved in Th1, Th2 and Th17 cell differentiation. In addition, four hub genes, BIRC5, PTPRC, PLEK, and FYN, were identified after selection and validation. These hub genes were subsequently shown to be closely associated with immune cells and related pathways. In NSCLC, PTPRC was downregulated, positively correlated with immune infiltration and immune cells. Experiments showed that PTPRC could promote the proliferation, migration and invasion, and the ability to form spheroids of A549 cells. In addition, PTPRC could regulate the increased expression of CD45, β-catenin, c-Myc and LEF1 proteins. This study explored the hub genes and related mechanisms of RA and NSCLC, demonstrated the central role of the inflammatory response and the adaptive immune system, and identified PTPRC as an immune-related biomarker and potential therapeutic target for RA and NSCLC patients. In addition, PTPRC can significantly promote the proliferation, migration and invasion of A549 cells, and its mechanism may be to promote the EMT process by regulating the Wnt signaling pathway and promote cell stemness, which in turn has a promoting effect on A549 cells.