Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus

Abstract

Yu Liu,1,* Enyi Zhu,1,* Yan Lei,1,* Ailing Luo,2 Yaping Yan,2 Mansi Cai,2 Shanshan Liu,2 Yan Huang,3 Hui Guan,1 Ming Zhong,1 Weinian Li,4 Lian Lin,1 Michael Hultstöm,5,6 Enyin Lai,7 Zhihua Zheng,1 Xiaoping Liu,2 Chun Tang1 1Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 2Department of Hematology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China; 3The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Rheumatology, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, 510623, People’s Republic of China; 5Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden; 6Department of Medical Cell Biology, Unit for Integrative Physiology, Uppsala University, Uppsala, Sweden; 7Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chun Tang; Xiaoping Liu, Email [email protected]; [email protected]: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.Keywords: methyltransferase like 1, systemic lupus erythematosus, immunity, single sample gene set enrichment analysis, biomarker

Keywords

• methyltransferase like 1
• systemic lupus erythematosus
• immunity
• single sample gene set enrichment analysis
• biomarker