Mendelian randomisation and bioinformatics-based analysis of the relationship between cervical cancer and rheumatoid arthritis and key genes,pathways and potential drugs
Objective To search for causal associations between cervical cancer and rheumatoid arthritis using Mendelian randomisation,and to search for genetic associations between the two diseases using bioinformatics to obtain po-tential therapeutic targets.These two methods will elucidate the possible effects of rheumatoid arthritis on cervical cancer and identify genetic targets that interact between the two diseases,providing ideas for disease treatment and new drug development.Methods Rheumatoid arthritis(ukb-b-11874)and cervical cancer(ukb-b-8777)were used as exposure factors and outcome variables,respectively,and SNPs with significant correlation with rheumatoid arthritis were selected as instrumental variables,and IVW,WME,Simple Mode,Weighted Mode and MR-Egger regression methods were used for the MR analysis,and het-erogeneity was analysed using Cochran Q test.One dataset each of cervical cancer and rheumatoid arthritis was downloaded from the GEO database and screened for DEGs,and the DEGs common to both diseases were subjected to GO functional an-notation and KEGG pathway enrichment analysis.PPI networks were constructed to identify the central genes of the two dis-eases.A drug signature database(DSigDB)was used to find potential therapeutic agents.Results A total of 3 SNPs were screened as instrumental variables,and the IVW results showed that rheumatoid arthritis was a risk factor for the risk of cer-vical cancer(OR=1.575＞1,P＜0.05).MR-Egger,WME,Simple Mode,Weighted Mode effect estimates had similar statistical results.Sensitivity analyses revealed that there were no SNPs that had a significant impact on the causal estimates.By inte-grating the two datasets of cervical cancer and rheumatoid arthritis,53 DEGs were obtained,8 central genes associated with the two diseases were identified,and potential therapeutic drugs for cervical cancer and rheumatoid arthritis were identified based on potential therapeutic targets.Conclusion This study demonstrated a causal relationship between rheumatoid arthritis and the risk of cervical cancer by Mendelian randomisation study methods,and bioinformatics methods further demonstrated a significant genetic association between the two diseases.The identified genes,pathways and drugs provide new ideas for the diagnosis and treatment of the two diseases in clinical work.
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