To explore the molecular mechanisms and shared genetic characteristics of rheumatoid arthritis and cervical cancer based on multiple omics and clinical samples.

OBJECTIVE: The potential association between rheumatoid arthritis (RA) and cervical cancer risk is still debated and necessitates additional clinical investigations. This study aimed to explore this relationship using Mendelian randomization and multi-omics analysis, aiming to enhance insights and reduce redundancy. METHODS: This study employs a Mendelian randomization approach to investigate potential associations between rheumatoid arthritis (RA) and cervical cancer susceptibility. Single-cell enrichment scores were calculated using RA-specific transcriptome differentially expressed genes, and prognostic models were developed using 10 machine learning algorithms to assess cervical cancer differential gene expression associated with RA scores. Subsequently, differences in clinical characteristics, immune cell infiltration, immunotherapy efficacy, and response to chemotherapeutic drugs were analyzed between high- and low-risk groups of patients. Finally, the expression of model genes was verified by cervical cancer cell lines and clinical fresh samples. RESULTS: Mendelian randomization has revealed an increased incidence of cervical cancer associated with RA. RA enrichment scores show predominant enrichment in the single-cell NK cell subpopulation. Cervical cancer can be distinctly categorized into two subgroups based on RA score-associated prognostic genes, demonstrating significant differences in immune cell infiltration and prognosis between these subgroups. Prognostic modeling indicates that patients in the low-risk group exhibit better prognosis, enhanced immune cell infiltration, and improved response to immunotherapy and drug treatments. Finally, multiple external data confirmed that there were significant differences in the expression of model genes. CONCLUSION: Rheumatoid arthritis is causally associated with the development of cervical cancer. Patients with rheumatoid arthritis have an increased risk of concurrent cervical cancer. Immune cell pathways, such as NK cell-based, may be important in increasing the risk of cervical cancer in RA patients. The abnormal expression of the model gene may be involved in the progression of cervical cancer patients and the impact of immunotherapy.