Genetic association and single-cell transcriptome analyses reveal distinct features connecting autoimmunity with cancers
Shasha Li,
Chenyang Lu,
Yuan Zhang,
Xiaolu Zhao,
Kequan Lin,
Xiufang Kong,
David Fox,
Lixiang Xue,
Lichao Sun,
Yi Liu,
Fengbiao Mao
Affiliations
Shasha Li
Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China
Chenyang Lu
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China; Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Laboratory of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
Yuan Zhang
Pharmacy Department, Zichuan District Hospital, Zichuan, Shandong 255100, China
Xiaolu Zhao
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
Kequan Lin
School of Life Sciences, Tsinghua University, Beijing 100084, China
Xiufang Kong
Department of Rheumatology and Immunology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
David Fox
Division of Rheumatology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Lixiang Xue
Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China; Cancer Center, Peking University Third Hospital, Beijing 100191, China
Lichao Sun
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Corresponding author
Yi Liu
Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China; Corresponding author
Fengbiao Mao
Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China; Cancer Center, Peking University Third Hospital, Beijing 100191, China; Corresponding author
Summary: Autoimmune diseases (ADs) are at a significantly higher risk of cancers with unclear mechanism. By searching GWAS catalog database and Medline, susceptible genes for five common ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren syndrome, systemic sclerosis, and idiopathic inflammatory myopathies, were collected and then were overlapped with cancer driver genes. Single-cell transcriptome analysis was performed in the comparation between 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 stemness 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.
