Super-Omics and PCAS Reveal Rheumatoid Arthritis as a Tumor-like Disease

Rheumatoid arthritis (RA) is a debilitating systemic autoimmune disorder that significantly impairs quality of life. To elucidate the molecular alterations driving RA progression, we performed comprehensive super-omics analyses on synovial tissues from patients with joint trauma, arthritis, and RA. These analyses included transcriptomics, proteomics, metabolomics, microbiomics, and fourteen PTMs (phosphorylation, acetylation, lactylation, O-GlcNAc glycosylation, arginine monomethylation, lysine monomethylation, lysine dimethylation, lysine trimethylation, succinylation, malonylation, glutarylation, tyrosine nitration, N-glycosylation, and O-glycosylation). Additionally, we developed a protein-centered association study (PCAS) method to integrate these complex datasets. Using this approach, we identified key proteins, such as STK17B, and its interactors, which may be crucial in RA pathogenesis. Tumor-like features, including aberrant angiogenesis and epithelial-mesenchymal transition, were observed in RA, alongside the potential involvement of oncogenes and tumor suppressor genes. Finally, we constructed a molecular interaction map of RA, providing a comprehensive framework for advancing RA pathogenesis, diagnosis, and therapy. Overall design: We selected 6 cases each of trauma patients, arthritis patients, and rheumatoid arthritis patients. Synovial tissue was obtained by removing the fat tissue from the joint capsule samples surgically excised from the patients. RNA was then extracted from the synovial tissue for gene expression sequencing, and the differences in gene expression among the three types of synovial tissue were analyzed.