IDENTIFICATION OF HUB GENES AND NEUTROPHIL REGULATORY PATHWAY IN PRIMARY ANTIPHOSPHOLIPID SYNDROME

Abstract

PAPS is a autoimmune disorder characterized by presence of aPL, which are main cause of repeated thrombotic complications. Earlier Antiphospholipid Syndrome (APS) was mainly detected in Individuals with pre-existing autoimmune pathologies such rheumatoid arthritis or systemic lupus erythematosus. One of the key mechanisms for thrombosis in PAPS is reported to be NETosis. This study focuses on identification of key hub genes and constructing a microRNA (miRNA) messenger RNA (mRNA) in PAPS, primarily focusing on Neutrophil cells. Differentially expressed mRNA (DE-mRNA) in patients were taken from previous studies and systemically screened using differential gene expression data of GSE102215 dataset from GEO. A Total 2428 DEGs were obtained of which 955 were overexpressed and 1473 underexpressed, among the DEGs 2034 were found to be protein coding. The PPI network analysis disclosed top 10 consensus hub genes (STAT2, DDX58, MX1, IFIT3, IFIH1, ISG15, IRF7, EIF2AK2, STAT1, IFI35) identified by Cytoscape software using Maximal Clique Centrality (MCC) and Degree to rank nodes in the PPI interactions based on local topological features. The pathway and functional enrichment have done using Enrichr. 5 DE-miRNAs were obtained from published literature and their targets gene were identified via TarBase v9.0, out of 9782 miRNA target genes 1209 overlap with DEGs. A network between miRNA and hub genes was constructed which demonstrated most hub genes are regulated by hsa-mirna-146. In conclusion, several hub genes linked to PAPS were identified. New information on the underlying mechanisms of PAPS is provided by miRNA-mRNA network regulatory network that may be pertinent to pathogenesis of PAPS.