Identifying Key Genes and Their Associated Molecular Pathways in Lupus Nephritis-Osteoporosis: An In-Silico Analysis

Abstract

Nephritis and osteoporosis are debilitating medical conditions that significantly impact human health and reduce quality of life. To develop potential therapeutic strategies for these disorders necessitates understanding the genetic and molecular mechanisms. Here, we employed bioinformatics techniques purposed to find key genes and associated pathways responsible for nephritis-osteoporosis comorbidity. Six microarray datasets of systemic lupus erythematosus (SLE) and osteoporosis were retrieved from the Gene Expression Omnibus (GEO) database. Post normalization of data sets LIMMA package was utilized for differential expression analysis, among the datasets 44 differentially expressed genes (DEGs) were identified. The identified 44 genes were further analyzed for gene ontology (GO) where it was found that these genes are involved in defense response, organism interactions, and response to external stimuli. In predicting the molecular function, they were involved in several biological processes including binding to lipopolysaccharides and having peptidase and hydrolase activities. Firstly, the identified genes were primarily associated with certain granules such as specific granules and secretory granules in the aspect of cellular components. Enrichment analysis pointed out the potential pathways linked to the immune system, neutrophil degranulation, innate immunity, and immune response to tuberculosis. To examine interactions among DEGs, a complex protein-protein interaction (PPI) network was built, resulting in the identification of seven hub genes, CXCL8, ELANE, LCN2, MMP8, IFIT1, MX1, and ISG15. The study suggests that these elucidated hub genes might have high potential to be exploited as promising biomarkers and therapeutic targets in nephritis-osteoporosis. Taken together, this study provided deeper insights into the genetic and molecular basis for the comorbidity of nephritis and osteoporosis.