Genetic association and single-cell transcriptome analyses reveal distinct features connecting autoimmunity with cancers

Autoimmune diseases (ADs) are at a significantly higher risk of cancers with un-clear mechanism. By searching GWAS catalog database and Medline, susceptible genes for five common ADs, including systemic lupus erythematosus (SLE), rheu-matoid arthritis, Sj??gren syndrome, systemic sclerosis, and idiopathic inflamma-tory myopathies, were collected and then were overlapped with cancer driver genes. Single-cell transcriptome analysis was performed in the comparation be-tween SLE and related cancer. We identified 45 carcinogenic autoimmune disease risk (CAD) genes, which were mainly enriched in T cell signaling pathway and B cell signaling pathway. Integrated single-cell analysis revealed immune cell signaling was significantly downregulated in renal cancer compared with SLE, while stem-ness signature was significantly enriched in both renal cancer or lymphoma and SLE in specific subpopulations. Drugs targeting CAD genes were shared between ADs and cancer. Our study highlights the common and specific features between ADs and related cancers, and sheds light on a new discovery of treatments.